{"entity": "researcher", "timestamp": "2026-08-10T17:13:19.358Z", "family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "affiliations": ["Department of Oncology-Pathology, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581"}}, "publications": [{"entity": "publication", "iuid": "7678863661af4b02bfe0ee23fb363270", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7678863661af4b02bfe0ee23fb363270.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7678863661af4b02bfe0ee23fb363270"}}, "title": "FOCU.SE trial: a nationwide Swedish drug repurposing protocol and research framework.", "authors": [{"family": "Abel", "given": "Edvard", "initials": "E", "orcid": "0000-0002-0482-2015", "researcher": {"href": "https://publications.scilifelab.se/researcher/81783c77012447f6b5c31566c55b295a.json"}}, {"family": "\u00d6stling", "given": "P\u00e4ivi", "initials": "P", "orcid": "0000-0001-5501-466X", "researcher": {"href": "https://publications.scilifelab.se/researcher/0461a910ec4b4faa8668bb4044e76f61.json"}}, {"family": "Hallersj\u00f6 Hult", "given": "Ebba", "initials": "E", "orcid": "0009-0005-7247-9510", "researcher": {"href": "https://publications.scilifelab.se/researcher/30edff4b6ada40898b84949cf6b69129.json"}}, {"family": "Kulbacka", "given": "Katarzyna", "initials": "K", "orcid": "0000-0002-9195-2300", "researcher": {"href": "https://publications.scilifelab.se/researcher/0d6b46c4fb77409683adc0dfe6f5c6cf.json"}}, {"family": "Babacic", "given": "Haris", "initials": "H"}, {"family": "Baan", "given": "Annika", "initials": "A"}, {"family": "Carneiro", "given": "Ana", "initials": "A"}, {"family": "De Petris", "given": "Luigi", "initials": "L"}, {"family": "Fagman", "given": "Henrik", "initials": "H"}, {"family": "Friesland", "given": "Signe", "initials": "S"}, {"family": "Frisell", "given": "Oskar", "initials": "O"}, {"family": "Hellstr\u00f6m", "given": "Mats", "initials": "M"}, {"family": "Lindahl", "given": "Gabriel", "initials": "G"}, {"family": "Steen Carlsson", "given": "Katarina", "initials": "K"}, {"family": "Tamborero", "given": "David", "initials": "D"}, {"family": "Valachis", "given": "Antonios", "initials": "A"}, {"family": "\u00d6hlund", "given": "Daniel", "initials": "D", "orcid": "0000-0002-5847-2778", "researcher": {"href": "https://publications.scilifelab.se/researcher/42e9e473f68c460098a37e22d0a41369.json"}}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Rosenquist", "given": "Richard", "initials": "R", "orcid": "0000-0002-0211-8788", "researcher": {"href": "https://publications.scilifelab.se/researcher/b570128e641140fb964ae3241414f510.json"}}, {"family": "Edsj\u00f6", "given": "Anders", "initials": "A", "orcid": "0000-0001-8783-8284", "researcher": {"href": "https://publications.scilifelab.se/researcher/6fae25d88855440194b9bb11b3d18bf8.json"}}, {"family": "FOCU.SE trial group", "given": "", "initials": ""}], "type": "journal article", "published": "2026-04-13", "journal": {"title": "Acta Oncol", "issn": "1651-226X", "volume": "65", "issn-l": "0284-186X"}, "abstract": null, "doi": "10.2340/ao.v65.45355", "pmid": "41972845", "labels": {"Clinical Genomics": "Collaborative", "Clinical Genomics Uppsala": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC13081547"}], "notes": [], "created": "2026-08-07T07:54:51.078Z", "modified": "2026-08-07T07:54:51.332Z"}, {"entity": "publication", "iuid": "f3a1b1396edb4101b0575fbc43ec7415", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f3a1b1396edb4101b0575fbc43ec7415.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f3a1b1396edb4101b0575fbc43ec7415"}}, "title": "Comparative evaluation of Olink Explore 3072 and mass spectrometry with peptide fractionation for plasma proteomics.", "authors": [{"family": "Sissala", "given": "Noora", "initials": "N", "orcid": "0009-0000-0758-8140", "researcher": {"href": "https://publications.scilifelab.se/researcher/3a96666a6a2e478fbdd3cf33d7db1e74.json"}}, {"family": "Baba\u010di\u0107", "given": "Haris", "initials": "H", "orcid": "0000-0003-0813-0005", "researcher": {"href": "https://publications.scilifelab.se/researcher/45a1c5d3d2d34a9e96d112877632784c.json"}}, {"family": "Leo", "given": "Isabelle R", "initials": "IR", "orcid": "0000-0002-7627-6690", "researcher": {"href": "https://publications.scilifelab.se/researcher/21185d9c6a2343f189397cbbb95c6e71.json"}}, {"family": "Cao", "given": "Xiaofang", "initials": "X"}, {"family": "Forshed", "given": "Jenny", "initials": "J"}, {"family": "Eriksson", "given": "Lars E", "initials": "LE", "orcid": "0000-0001-5121-5325", "researcher": {"href": "https://publications.scilifelab.se/researcher/ebb717a9972245a5b2427a4b8421fe6f.json"}}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Fredolini", "given": "Claudia", "initials": "C", "orcid": "0000-0002-7674-2014", "researcher": {"href": "https://publications.scilifelab.se/researcher/40ac3a5823cb4f998cc8bdb96dcbf195.json"}}, {"family": "\u00c5berg", "given": "Mikael", "initials": "M", "orcid": "0000-0002-7858-8233", "researcher": {"href": "https://publications.scilifelab.se/researcher/90fa86e9aeaa43ea9547e48b4f3f24e3.json"}}, {"family": "Pernemalm", "given": "Maria", "initials": "M", "orcid": "0000-0003-4624-031X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f15f303cb2044cfa81719700137e3603.json"}}], "type": "journal article", "published": "2025-11-04", "journal": {"title": "Commun Chem", "issn": "2399-3669", "issn-l": null, "volume": "8", "issue": "1", "pages": "327"}, "abstract": "Plasma proteomics technologies are advancing rapidly, offering new opportunities for biomarker discovery and precision medicine. Direct comparisons of available technologies are needed to understand how platform selection affects downstream findings. We compared the performance of a peptide fractionation-based mass spectrometry method (HiRIEF LC-MS/MS) and the Olink Explore 3072 proximity extension assays on 88 plasma samples, analyzing 1129 proteins with both methods. The platforms exhibited complementary proteome coverage, high precision, and concordance in estimating sex differences in protein levels. Quantitative agreement between platforms was moderate (median correlation 0.59, interquartile range 0.33-0.75), mainly influenced by technical factors. Finally, we present a publicly available tool for peptide-level analysis of platform agreement and demonstrate its utility in clarifying cross-platform discrepancies in protein and proteoform measurements. Our findings provide insights for platform selection and study design, and highlight the value of combining mass spectrometry and affinity-based approaches for more comprehensive and reliable plasma proteome profiling.", "doi": "10.1038/s42004-025-01753-2", "pmid": "41188494", "labels": {"National Genomics Infrastructure": "Service", "NGI Proteomics": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Affinity Proteomics Stockholm": "Collaborative", "Affinity Proteomics Uppsala": "Collaborative", "Global Proteomics and Proteogenomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12586489"}, {"db": "pii", "key": "10.1038/s42004-025-01753-2"}], "notes": [], "created": "2025-11-07T07:35:27.214Z", "modified": "2025-11-27T13:03:30.885Z"}, {"entity": "publication", "iuid": "d393109fcd1c4ba9be1fc99ed851ad05", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d393109fcd1c4ba9be1fc99ed851ad05.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d393109fcd1c4ba9be1fc99ed851ad05"}}, "title": "In-depth patient-specific analysis of tumor heterogeneity in melanoma brain metastasis: Insights from spatial transcriptomics and multi-region bulk sequencing.", "authors": [{"family": "Sharma", "given": "Nidhi", "initials": "N", "orcid": "0000-0002-2475-9340", "researcher": {"href": "https://publications.scilifelab.se/researcher/eadc0f3bfb5443e8a14af7d785085324.json"}}, {"family": "R\u00e1jov\u00e1", "given": "Jana", "initials": "J"}, {"family": "Mermelekas", "given": "Georgios", "initials": "G"}, {"family": "Thrane", "given": "Kim", "initials": "K", "orcid": "0000-0003-3109-5551", "researcher": {"href": "https://publications.scilifelab.se/researcher/f1bd1b94e1694de9a5c27fd8f331dc86.json"}}, {"family": "Lundeberg", "given": "Joakim", "initials": "J", "orcid": "0000-0003-4313-1601", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a4e6ca0f29b4ead8569e2729481c3e0.json"}}, {"family": "Shamikh", "given": "Alia", "initials": "A"}, {"family": "Vikstr\u00f6m", "given": "Sofi", "initials": "S"}, {"family": "Baba\u010di\u0107", "given": "Haris", "initials": "H", "orcid": "0000-0003-0813-0005", "researcher": {"href": "https://publications.scilifelab.se/researcher/45a1c5d3d2d34a9e96d112877632784c.json"}}, {"family": "Jensdottir", "given": "Margret", "initials": "M"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Pernemalm", "given": "Maria", "initials": "M", "orcid": "0000-0003-4624-031X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f15f303cb2044cfa81719700137e3603.json"}}, {"family": "Eriksson", "given": "Hanna", "initials": "H"}], "type": "journal article", "published": "2025-09-00", "journal": {"title": "Transl Oncol", "issn": "1936-5233", "volume": "59", "pages": "102468", "issn-l": null}, "abstract": "Melanoma brain metastases (MBM) exhibit extensive intertumor and intratumor heterogeneity (ITH), driven by a complex tumor microenvironment. The aim of this study was to perform a detailed analysis of individual MBM patient tumors using a multiomics approach, integrating spatial transcriptomics with multi-region bulk exome, proteome, and transcriptome profiling for a small group of four patient samples. We identified significant patient-specific variations in immune cell infiltration, particularly in B/plasma cells, myeloid cells, and cancer-associated fibroblasts (CAFs). Notably, immunotherapy-treated patients showed enriched pathways related to epithelial-mesenchymal transition (EMT), interferon-gamma (IFN-\u03b3) signaling, oxidative phosphorylation, T-cell signaling, inflammation and DNA damage, which aligned with distinct cellular compositions observed in the spatial analysis. We also uncovered considerable ITH, especially at the protein level, revealing differential expression patterns of key tumor and immune-related markers. The correlation between mRNA and protein data highlighted consistent enrichment of critical pathways across multiomics layers. These findings highlight the molecular and cellular landscape of individual patient MBM, underscoring the importance of addressing tumor heterogeneity in the development of effective therapeutic strategies.", "doi": "10.1016/j.tranon.2025.102468", "pmid": "40669378", "labels": {"NGI Short read": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12284558"}, {"db": "pii", "key": "S1936-5233(25)00199-8"}], "notes": [], "created": "2025-07-18T10:25:23.220Z", "modified": "2025-11-28T10:44:36.443Z"}, {"entity": "publication", "iuid": "5753418da8414fd289afbad0fb47aa21", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5753418da8414fd289afbad0fb47aa21.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5753418da8414fd289afbad0fb47aa21"}}, "title": "Pathway activation model for personalized prediction of drug synergy.", "authors": [{"family": "Trac", "given": "Quang Thinh", "initials": "QT", "orcid": "0000-0003-2429-0287", "researcher": {"href": "https://publications.scilifelab.se/researcher/043294bad46e4ccaa3d0d7cd43ebdccd.json"}}, {"family": "Huang", "given": "Yue", "initials": "Y"}, {"family": "Erkers", "given": "Tom", "initials": "T"}, {"family": "\u00d6stling", "given": "P\u00e4ivi", "initials": "P"}, {"family": "Bohlin", "given": "Anna", "initials": "A"}, {"family": "Osterroos", "given": "Albin", "initials": "A"}, {"family": "Vesterlund", "given": "Mattias", "initials": "M", "orcid": "0000-0001-9471-6592", "researcher": {"href": "https://publications.scilifelab.se/researcher/0942e438993b494db2a3db914852c808.json"}}, {"family": "Jafari", "given": "Rozbeh", "initials": "R"}, {"family": "Siavelis", "given": "Ioannis", "initials": "I"}, {"family": "Backvall", "given": "Helena", "initials": "H"}, {"family": "Kiviluoto", "given": "Santeri", "initials": "S"}, {"family": "Orre", "given": "Lukas", "initials": "L"}, {"family": "Rantalainen", "given": "Mattias", "initials": "M"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Lehmann", "given": "Soren", "initials": "S"}, {"family": "Kallioniemi", "given": "Olli", "initials": "O"}, {"family": "Pawitan", "given": "Yudi", "initials": "Y"}, {"family": "Vu", "given": "Trung Nghia", "initials": "TN", "orcid": "0000-0001-7945-5750", "researcher": {"href": "https://publications.scilifelab.se/researcher/d90993bc42694d969a24a50f21393b76.json"}}], "type": "journal article", "published": "2025-06-03", "journal": {"title": "Elife", "issn": "2050-084X", "volume": "13", "issn-l": "2050-084X"}, "abstract": "Targeted monotherapies for cancer often fail due to inherent or acquired drug resistance. By aiming at multiple targets simultaneously, drug combinations can produce synergistic interactions that increase drug effectiveness and reduce resistance. Computational models based on the integration of omics data have been used to identify synergistic combinations, but predicting drug synergy remains a challenge. Here, we introduce Drug synergy Interaction Prediction (DIPx), an algorithm for personalized prediction of drug synergy based on biologically motivated tumor- and drug-specific pathway activation scores (PASs). We trained and validated DIPx in the AstraZeneca-Sanger (AZS) DREAM Challenge human cell-line dataset using two separate test sets: Test Set 1 comprised the combinations already present in the training set, while Test Set 2 contained combinations absent from the training set, thus indicating the model's ability to handle novel combinations. The Spearman's correlation coefficients between predicted and observed drug synergy were 0.50 (95% CI: 0.47-0.53) in Test Set 1 and 0.26 (95% CI: 0.22-0.30) in Test Set 2, compared to 0.38 (95% CI: 0.34-0.42) and 0.18 (95% CI: 0.16-0.20), respectively, for the best performing method in the Challenge. We show evidence that higher synergy is associated with higher functional interaction between the drug targets, and this functional interaction information is captured by PAS. We illustrate the use of PAS to provide a potential biological explanation in terms of activated pathways that mediate the synergistic effects of combined drugs. In summary, DIPx can be a useful tool for personalized prediction of drug synergy and exploration of activated pathways related to the effects of combined drugs.", "doi": "10.7554/eLife.100071", "pmid": "40459126", "labels": {"Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12133153"}, {"db": "pii", "key": "100071"}], "notes": [], "created": "2025-11-28T10:54:44.321Z", "modified": "2025-11-28T10:54:44.431Z"}, {"entity": "publication", "iuid": "b5cadf33662a43ba963d6e97bfa96d3a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b5cadf33662a43ba963d6e97bfa96d3a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b5cadf33662a43ba963d6e97bfa96d3a"}}, "title": "Precision Omics Initiative Sweden (PROMISE) will integrate research with healthcare.", "authors": [{"family": "K\u00e4mpe", "given": "Anders", "initials": "A", "orcid": "0000-0002-1829-3855", "researcher": {"href": "https://publications.scilifelab.se/researcher/0785e17b57384962a0ff9bc7ecaa80c8.json"}}, {"family": "Gudmundsson", "given": "Sanna", "initials": "S"}, {"family": "Walsh", "given": "Colum P", "initials": "CP"}, {"family": "Lindblad-Toh", "given": "Kerstin", "initials": "K"}, {"family": "Johansson", "given": "\u00c5sa", "initials": "\u00c5", "orcid": "0000-0002-2915-4498", "researcher": {"href": "https://publications.scilifelab.se/researcher/76265c54961046e99bdb0439f9ae1d34.json"}}, {"family": "Clareborn", "given": "Anna", "initials": "A"}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}, {"family": "Edsj\u00f6", "given": "Anders", "initials": "A", "orcid": "0000-0001-8783-8284", "researcher": {"href": "https://publications.scilifelab.se/researcher/6fae25d88855440194b9bb11b3d18bf8.json"}}, {"family": "Fioretos", "given": "Thoas", "initials": "T"}, {"family": "Ehrencrona", "given": "Hans", "initials": "H", "orcid": "0000-0002-5589-3622", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b89608a8ce941c3b9911630b4ff9720.json"}}, {"family": "Eriksson", "given": "Daniel", "initials": "D", "orcid": "0000-0001-5473-3312", "researcher": {"href": "https://publications.scilifelab.se/researcher/f9c26578a5e548f783b9465e04fb0bfc.json"}}, {"family": "Fall", "given": "Tove", "initials": "T", "orcid": "0000-0003-2071-5866", "researcher": {"href": "https://publications.scilifelab.se/researcher/4ed3f066719f43b291743a8bdaf3d2a0.json"}}, {"family": "Franks", "given": "Paul W", "initials": "PW", "orcid": "0000-0002-0520-7604", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ebbf40c0f7e49dd8c75a2b6cbf27276.json"}}, {"family": "Gyllensten", "given": "Ulf", "initials": "U", "orcid": "0000-0002-6316-3355", "researcher": {"href": 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"initials": "A"}, {"family": "Wirta", "given": "Valtteri", "initials": "V", "orcid": "0000-0003-3811-5439", "researcher": {"href": "https://publications.scilifelab.se/researcher/cba024b2e3c347f6b981922d984ad2d6.json"}}, {"family": "\u00d6stling", "given": "P\u00e4ivi", "initials": "P"}, {"family": "Jacobsson", "given": "Bo", "initials": "B", "orcid": "0000-0001-5079-2374", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd6968816ded4a50b1029ee3f4afbeed.json"}}, {"family": "Sj\u00f6blom", "given": "Tobias", "initials": "T", "orcid": "0000-0001-6668-4140", "researcher": {"href": "https://publications.scilifelab.se/researcher/909f00a5bf6e465f9ff560b12bcd863a.json"}}, {"family": "Persson", "given": "Bengt", "initials": "B"}, {"family": "Rosenquist", "given": "Richard", "initials": "R", "orcid": "0000-0002-0211-8788", "researcher": {"href": "https://publications.scilifelab.se/researcher/b570128e641140fb964ae3241414f510.json"}}, {"family": "Lindstrand", "given": "Anna", "initials": "A", "orcid": "0000-0003-0806-5602", "researcher": {"href": "https://publications.scilifelab.se/researcher/07f3e6152da043d38c7a81974fcf8c23.json"}}, {"family": "Lappalainen", "given": "Tuuli", "initials": "T"}], "type": "letter", "published": "2025-06-00", "journal": {"title": "Nat. Med.", "issn": "1546-170X", "issn-l": "1078-8956", "volume": "31", "issue": "6", "pages": "1730-1732"}, "abstract": null, "doi": "10.1038/s41591-025-03631-9", "pmid": "40186080", "labels": {"Clinical Genomics Gothenburg": "Collaborative", "National Genomics Infrastructure": "Collaborative", "NGI Uppsala (Uppsala Genome Center)": "Collaborative", "NGI Long read": "Collaborative", "Clinical Genomics Lund": "Service", "Bioinformatics (NBIS)": "Collaborative", "Bioinformatics Support, Infrastructure and Training": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41591-025-03631-9"}], "notes": [], "created": "2025-07-08T13:55:07.435Z", "modified": "2025-11-21T13:21:42.346Z"}, {"entity": "publication", "iuid": "ff82f6f4bfb34c93a66ea6b5c6e6a9f0", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ff82f6f4bfb34c93a66ea6b5c6e6a9f0.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ff82f6f4bfb34c93a66ea6b5c6e6a9f0"}}, "title": "The non-canonical BAF chromatin remodeling complex is a novel target of spliceosome dysregulation in SF3B1-mutated chronic lymphocytic leukemia.", "authors": [{"family": "H\u00e4gerstrand", "given": "Daniel", "initials": "D", "orcid": "0000-0001-7270-0776", "researcher": {"href": "https://publications.scilifelab.se/researcher/35a683cea1874ac290d91c325a648be8.json"}}, {"family": "Oder", "given": "Bla\u017e", "initials": "B", "orcid": "0000-0001-7984-3104", "researcher": {"href": "https://publications.scilifelab.se/researcher/9851f9fc65fc44aea55d0c1567be7887.json"}}, {"family": "Cortese", "given": "Diego", "initials": "D"}, {"family": "Qu", "given": "Ying", "initials": "Y"}, {"family": "Binzer-Panchal", "given": "Amrei", "initials": "A", "orcid": "0000-0002-0472-0609", "researcher": {"href": "https://publications.scilifelab.se/researcher/9b6fe18ad8f8495a97d9322cac3201da.json"}}, {"family": "\u00d6sterholm", "given": "Cecilia", "initials": "C"}, {"family": "Del Peso Santos", "given": "Teresa", "initials": "T"}, {"family": "Rabbani", "given": "Leily", "initials": "L"}, {"family": "Asl", "given": "Hassan Foroughi", "initials": "HF"}, {"family": "Skaftason", "given": "Aron", "initials": "A"}, {"family": "Ljungstr\u00f6m", "given": "Viktor", "initials": "V"}, {"family": "Lundholm", "given": "August", "initials": "A"}, {"family": "Koutroumani", "given": "Maria", "initials": "M"}, {"family": "Haider", "given": "Zahra", "initials": "Z"}, {"family": "Jylh\u00e4", "given": "Cecilia", "initials": "C"}, {"family": "Mollstedt", "given": "John", "initials": "J"}, {"family": "Mansouri", "given": "Larry", "initials": "L"}, {"family": "Plevova", "given": "Karla", "initials": "K"}, {"family": "Agathangelidis", "given": "Andreas", "initials": "A", "orcid": "0000-0002-8467-7945", "researcher": {"href": "https://publications.scilifelab.se/researcher/79eb64984ac1494094f8c632b18bc793.json"}}, {"family": "Scarf\u00f2", "given": "Lydia", "initials": "L", "orcid": "0000-0002-0844-0989", "researcher": {"href": "https://publications.scilifelab.se/researcher/47c4c336efb24d86b41c872d03836c78.json"}}, {"family": "Armand", "given": "Marine", "initials": "M", "orcid": "0000-0001-8906-3128", "researcher": {"href": "https://publications.scilifelab.se/researcher/8d2e8c325db8415cb723a9718d49ae78.json"}}, {"family": "Muggen", "given": "Alice F", "initials": "AF"}, {"family": "Kay", "given": "Neil E", "initials": "NE", "orcid": "0000-0002-5951-5055", "researcher": {"href": "https://publications.scilifelab.se/researcher/ef074d0fdb0b4070b5216be063317bf8.json"}}, {"family": "Shanafelt", "given": "Tait", "initials": "T"}, {"family": "Rossi", "given": "Davide", "initials": "D"}, {"family": "Orre", "given": "Lukas M", "initials": "LM", "orcid": "0000-0002-0384-1003", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b4e49a93b0143db88059c4d1e9fdc59.json"}}, {"family": "Pospisilova", "given": "Sarka", "initials": "S", "orcid": "0000-0001-7136-2680", "researcher": {"href": "https://publications.scilifelab.se/researcher/241cf7f1344c4016b40dfcf439c0b43d.json"}}, {"family": "Barylyuk", "given": "Konstantin", "initials": "K", "orcid": "0000-0002-3580-0345", "researcher": {"href": "https://publications.scilifelab.se/researcher/f5db39fce380438e82060c586e230ee6.json"}}, {"family": "Davi", "given": "Frederic", "initials": "F"}, {"family": "Vesterlund", "given": "Mattias", "initials": "M", "orcid": "0000-0001-9471-6592", "researcher": {"href": "https://publications.scilifelab.se/researcher/0942e438993b494db2a3db914852c808.json"}}, {"family": "Langerak", "given": "Anton W", "initials": "AW", "orcid": "0000-0002-2078-3220", "researcher": {"href": "https://publications.scilifelab.se/researcher/769a5b06013b43d6af8d3e13804cd50c.json"}}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Ghia", "given": "Paolo", "initials": "P", "orcid": "0000-0003-3750-7342", "researcher": {"href": "https://publications.scilifelab.se/researcher/46f24783739d44c7b73a1be28c344a35.json"}}, {"family": "Stamatopoulos", "given": "Kostas", "initials": "K", "orcid": "0000-0001-8529-640X", "researcher": {"href": "https://publications.scilifelab.se/researcher/772756566c154559b2c70c8f0f44d1ad.json"}}, {"family": "Sutton", "given": "Lesley-Ann", "initials": "LA"}, {"family": "Rosenquist", "given": "Richard", "initials": "R", "orcid": "0000-0002-0211-8788", "researcher": {"href": "https://publications.scilifelab.se/researcher/b570128e641140fb964ae3241414f510.json"}}], "type": "journal article", "published": "2024-11-00", "journal": {"title": "Leukemia", "issn": "1476-5551", "volume": "38", "issue": "11", "pages": "2429-2442", "issn-l": "0887-6924"}, "abstract": "SF3B1 mutations are recurrent in chronic lymphocytic leukemia (CLL), particularly enriched in clinically aggressive stereotyped subset #2. To investigate their impact, we conducted RNA-sequencing of 18 SF3B1MUT and 17 SF3B1WT subset #2 cases and identified 80 significant alternative splicing events (ASEs). Notable ASEs concerned exon inclusion in the non-canonical BAF (ncBAF) chromatin remodeling complex subunit, BRD9, and splice variants in eight additional ncBAF complex interactors. Long-read RNA-sequencing confirmed the presence of splice variants, and extended analysis of 139 CLL cases corroborated their association with SF3B1 mutations. Overexpression of SF3B1K700E induced exon inclusion in BRD9, resulting in a novel splice isoform with an alternative C-terminus. Protein interactome analysis of the BRD9 splice isoform revealed augmented ncBAF complex interaction, while exhibiting decreased binding of auxiliary proteins, including SPEN, BRCA2, and CHD9. Additionally, integrative multi-omics analysis identified a ncBAF complex-bound gene quartet on chromosome 1 with higher expression levels and more accessible chromatin in SF3B1MUT CLL. Finally, Cancer Dependency Map analysis and BRD9 inhibition displayed BRD9 dependency and sensitivity in cell lines and primary CLL cells. In conclusion, spliceosome dysregulation caused by SF3B1 mutations leads to multiple ASEs and an altered ncBAF complex interactome, highlighting a novel pathobiological mechanism in SF3B1MUT CLL.", "doi": "10.1038/s41375-024-02379-4", "pmid": "39261602", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service", "NGI Short read": "Service", "Bioinformatics Support for Computational Resources": "Service", "Global Proteomics and Proteogenomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11518989"}, {"db": "pii", "key": "10.1038/s41375-024-02379-4"}], "notes": [], "created": "2024-11-12T10:55:28.718Z", "modified": "2025-02-28T14:13:56.146Z"}, {"entity": "publication", "iuid": "d4cc256bef78493f8f58ebd4cad6618a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d4cc256bef78493f8f58ebd4cad6618a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d4cc256bef78493f8f58ebd4cad6618a"}}, "title": "Cancer Core Europe: Leveraging Institutional Synergies to Advance Oncology Research and Care Globally.", "authors": [{"family": "Carmona", "given": "Javier", "initials": "J", "orcid": "0000-0001-7904-8493", "researcher": {"href": "https://publications.scilifelab.se/researcher/98b34020208d4cea833bb3bd8e373733.json"}}, {"family": "Chavarria", "given": "Elena", "initials": "E", "orcid": "0009-0008-3182-8309", "researcher": {"href": "https://publications.scilifelab.se/researcher/838dfd51449d417b876287892d4c2914.json"}}, {"family": "Donoghue", "given": "Kate", "initials": "K", "orcid": "0000-0002-8715-9828", "researcher": {"href": "https://publications.scilifelab.se/researcher/f92b5174508b4edfb966f452e51ebfe8.json"}}, {"family": "von Gertten", "given": "Christina", "initials": "C", "orcid": "0009-0003-0029-3237", "researcher": {"href": "https://publications.scilifelab.se/researcher/9b619d65b0aa4285938dac2692eab82a.json"}}, {"family": "Oberrauch", "given": "Petra", "initials": "P", 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"researcher": {"href": "https://publications.scilifelab.se/researcher/740d488afc204156b682b67589992023.json"}}, {"family": "Wirta", "given": "Valtteri", "initials": "V", "orcid": "0000-0003-3811-5439", "researcher": {"href": "https://publications.scilifelab.se/researcher/cba024b2e3c347f6b981922d984ad2d6.json"}}, {"family": "Baird", "given": "Richard D", "initials": "RD", "orcid": "0000-0001-7071-6483", "researcher": {"href": "https://publications.scilifelab.se/researcher/11aa354bf2f74c4d8c31f3e0faf650db.json"}}, {"family": "Barker", "given": "Karen", "initials": "K", "orcid": "0009-0002-3334-5518", "researcher": {"href": "https://publications.scilifelab.se/researcher/63ffd01970e44c3486381dd71c098d94.json"}}, {"family": "Barlesi", "given": "Fabrice", "initials": "F", "orcid": "0000-0001-5793-3539", "researcher": {"href": "https://publications.scilifelab.se/researcher/2f4fa4b1ca0a4d4b89bbaab433fcc61d.json"}}, {"family": "Baumann", "given": "Michael", "initials": "M", "orcid": "0000-0002-9340-974X", "researcher": {"href": "https://publications.scilifelab.se/researcher/5d631ec8e65547d8a71940dabb52c83f.json"}}, {"family": "Bergh", "given": "Jonas", "initials": "J", "orcid": "0000-0001-5526-1847", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd38f4f7704144ed9e3f869e197175e6.json"}}, {"family": "de Braud", "given": "Filippo", "initials": "F", "orcid": "0000-0003-0103-730X", "researcher": {"href": "https://publications.scilifelab.se/researcher/87678aa063334710b4ab1a5b60a169ce.json"}}, {"family": "Fizazi", "given": "Karim", "initials": "K", "orcid": "0000-0002-6068-9474", "researcher": {"href": "https://publications.scilifelab.se/researcher/0a097ed3834e4d60af84b976a9e9a6ef.json"}}, {"family": "Fr\u00f6hling", "given": "Stefan", "initials": "S", "orcid": "0000-0001-7907-4595", "researcher": {"href": "https://publications.scilifelab.se/researcher/cd46d3f4c2084ce7922ceb0220b09277.json"}}, {"family": "Piris-Gim\u00e9nez", "given": "Alejandro", "initials": "A", "orcid": "0000-0002-7768-3722", "researcher": {"href": "https://publications.scilifelab.se/researcher/47494038256f4accad296c9f07414547.json"}}, {"family": "Seamon", "given": "Kenneth", "initials": "K", "orcid": "0009-0002-5418-9614", "researcher": {"href": "https://publications.scilifelab.se/researcher/2266a59a24de469db73f80325f453a1d.json"}}, {"family": "Van der Heijden", "given": "Michiel S", "initials": "MS", "orcid": "0000-0002-4407-7881", "researcher": {"href": "https://publications.scilifelab.se/researcher/b85df9575f734187bdcfabc26b5b875b.json"}}, {"family": "Zwart", "given": "Wilbert", "initials": "W", "orcid": "0000-0002-9823-7289", "researcher": {"href": "https://publications.scilifelab.se/researcher/0a374eac6b84402a8288748794d8074c.json"}}, {"family": "Tabernero", "given": "Josep", "initials": "J", "orcid": "0000-0002-2495-8139", "researcher": {"href": "https://publications.scilifelab.se/researcher/c9be0e16fc3f415e92754a6135bfc164.json"}}], "type": "journal article", "published": "2024-07-01", "journal": {"title": "Cancer Discov", "issn": "2159-8290", "volume": "14", "issue": "7", "pages": "1147-1153", "issn-l": null}, "abstract": "Cancer Core Europe brings together the expertise, resources, and interests of seven leading cancer institutes committed to leveraging collective innovation and collaboration in precision oncology. Through targeted efforts addressing key medical challenges in cancer and partnerships with multiple stakeholders, the consortium seeks to advance cancer research and enhance equitable patient care.", "doi": "10.1158/2159-8290.CD-24-0377", "pmid": "38870393", "labels": {"Clinical Genomics Stockholm": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "745892"}], "notes": [], "created": "2024-07-01T10:50:31.545Z", "modified": "2024-11-20T20:03:59.074Z"}, {"entity": "publication", "iuid": "d4db29d93f3144d29d7dcb207e5ed083", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d4db29d93f3144d29d7dcb207e5ed083.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d4db29d93f3144d29d7dcb207e5ed083"}}, "title": "Longitudinal molecular profiling elucidates immunometabolism dynamics in breast cancer.", "authors": [{"family": "Wang", "given": "Kang", "initials": "K", "orcid": "0000-0001-5401-1803", "researcher": {"href": "https://publications.scilifelab.se/researcher/7bdb074014224910b0f34e893b15e660.json"}}, {"family": "Zerdes", "given": "Ioannis", "initials": "I", "orcid": "0000-0002-8304-2462", "researcher": {"href": "https://publications.scilifelab.se/researcher/f786763a4a0e4b5bb865ebb199eb6ca2.json"}}, {"family": "Johansson", "given": "Henrik J", "initials": "HJ", "orcid": "0000-0003-4729-4205", "researcher": {"href": "https://publications.scilifelab.se/researcher/18aebf211fa640f48a7c8d860c168e5a.json"}}, {"family": "Sarhan", "given": "Dhifaf", "initials": "D", "orcid": "0000-0003-0196-4496", "researcher": {"href": "https://publications.scilifelab.se/researcher/22a235fbd46e49ba953ea339b8b8a507.json"}}, {"family": "Sun", "given": "Yizhe", "initials": "Y"}, {"family": "Kanellis", "given": "Dimitris C", "initials": "DC", "orcid": "0000-0001-8690-2010", "researcher": {"href": "https://publications.scilifelab.se/researcher/0921ab7566514fb0a3cd0daf2baabe6e.json"}}, {"family": "Sifakis", "given": "Emmanouil G", "initials": "EG", "orcid": "0000-0001-9919-4471", "researcher": {"href": "https://publications.scilifelab.se/researcher/c8506000a14a4a5286aa557ab67ef690.json"}}, {"family": "Mezheyeuski", "given": "Artur", "initials": "A"}, {"family": "Liu", "given": "Xingrong", "initials": "X"}, {"family": "Loman", "given": "Niklas", "initials": "N"}, {"family": "Hedenfalk", "given": "Ingrid", "initials": "I", "orcid": "0000-0002-6840-3397", "researcher": {"href": "https://publications.scilifelab.se/researcher/c852ed467120466f91d053425077c0b8.json"}}, {"family": "Bergh", "given": "Jonas", "initials": "J", "orcid": "0000-0001-5526-1847", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd38f4f7704144ed9e3f869e197175e6.json"}}, {"family": "Bartek", "given": "Jiri", "initials": "J", "orcid": "0000-0003-2013-7525", "researcher": {"href": "https://publications.scilifelab.se/researcher/cd0d4d98261f41268c76dd91345a1857.json"}}, {"family": "Hatschek", "given": "Thomas", "initials": "T"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Matikas", "given": "Alexios", "initials": "A", "orcid": "0000-0002-4122-9624", "researcher": {"href": "https://publications.scilifelab.se/researcher/0af6483a77d746c2b838414692f1f4ed.json"}}, {"family": "Foukakis", "given": "Theodoros", "initials": "T", "orcid": "0000-0001-8952-9987", "researcher": {"href": "https://publications.scilifelab.se/researcher/7683c0280e9b4145aa54305fb08936a7.json"}}], "type": "journal article", "published": "2024-05-07", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "15", "issue": "1", "pages": "3837", "issn-l": "2041-1723"}, "abstract": "Although metabolic reprogramming within tumor cells and tumor microenvironment (TME) is well described in breast cancer, little is known about how the interplay of immune state and cancer metabolism evolves during treatment. Here, we characterize the immunometabolic profiles of tumor tissue samples longitudinally collected from individuals with breast cancer before, during and after neoadjuvant chemotherapy (NAC) using proteomics, genomics and histopathology. We show that the pre-, on-treatment and dynamic changes of the immune state, tumor metabolic proteins and tumor cell gene expression profiling-based metabolic phenotype are associated with treatment response. Single-cell/nucleus RNA sequencing revealed distinct tumor and immune cell states in metabolism between cold and hot tumors. Potential drivers of NAC based on above analyses were validated in vitro. In summary, the study shows that the interaction of tumor-intrinsic metabolic states and TME is associated with treatment outcome, supporting the concept of targeting tumor metabolism for immunoregulation.", "doi": "10.1038/s41467-024-47932-y", "pmid": "38714665", "labels": {"Global Proteomics and Proteogenomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC11076527"}, {"db": "pii", "key": "10.1038/s41467-024-47932-y"}], "notes": [], "created": "2024-11-27T13:26:50.334Z", "modified": "2024-11-27T13:26:50.959Z"}, {"entity": "publication", "iuid": "8bfe93edf9d64769a9d6fef06df316a3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8bfe93edf9d64769a9d6fef06df316a3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8bfe93edf9d64769a9d6fef06df316a3"}}, "title": "Development of mesothelioma-specific oncolytic immunotherapy enabled by immunopeptidomics of murine and human mesothelioma tumors.", "authors": [{"family": "Chiaro", "given": "Jacopo", "initials": "J"}, {"family": "Antignani", "given": "Gabriella", "initials": "G"}, {"family": "Feola", "given": "Sara", "initials": "S", "orcid": "0000-0002-4012-4310", "researcher": {"href": "https://publications.scilifelab.se/researcher/c9d2c4168aa541b5ad9a7e5155dc1069.json"}}, {"family": "Feodoroff", "given": "Michaela", "initials": "M", "orcid": "0000-0002-6094-9838", "researcher": {"href": "https://publications.scilifelab.se/researcher/b828ef2f6621496cbc6ac77cc8413c14.json"}}, {"family": "Martins", "given": "Beatriz", "initials": "B"}, {"family": "Cojoc", "given": "Hanne", "initials": "H"}, {"family": "Russo", "given": "Salvatore", "initials": "S"}, {"family": "Fusciello", "given": "Manlio", "initials": "M", "orcid": "0000-0002-7166-3018", "researcher": {"href": "https://publications.scilifelab.se/researcher/4c74e3317cd646c1989a49b281c3e8e7.json"}}, {"family": "Hamdan", "given": "Firas", "initials": "F", "orcid": "0000-0003-4678-7382", "researcher": {"href": "https://publications.scilifelab.se/researcher/3f991da24d5c4c02945f0bfb614558a2.json"}}, {"family": "Ferrari", "given": "Valentina", "initials": "V"}, {"family": "Ciampi", "given": "Daniele", "initials": "D", "orcid": "0000-0001-6523-3049", "researcher": {"href": "https://publications.scilifelab.se/researcher/3161ddeb6095464fbd04afed3d7e56ee.json"}}, {"family": "Ilonen", "given": "Ilkka", "initials": "I", "orcid": "0000-0002-8149-3550", "researcher": {"href": "https://publications.scilifelab.se/researcher/8409282fff6b479daec8aa4e898a3aee.json"}}, {"family": "R\u00e4s\u00e4nen", "given": "Jari", "initials": "J"}, {"family": "M\u00e4yr\u00e4np\u00e4\u00e4", "given": "Mikko", "initials": "M", "orcid": "0000-0002-0877-9640", "researcher": {"href": "https://publications.scilifelab.se/researcher/63d6deb5a00141b0bb2c2f031ef8d53a.json"}}, {"family": "Partanen", "given": "Jukka", "initials": "J", "orcid": "0000-0001-6681-4734", "researcher": {"href": "https://publications.scilifelab.se/researcher/5f3b7cf9d4874b63b92556eccf060493.json"}}, {"family": "Koskela", "given": "Satu", "initials": "S", "orcid": "0000-0001-9258-9163", "researcher": {"href": "https://publications.scilifelab.se/researcher/478c0a65a147450bb5c5a7ba7d196b41.json"}}, {"family": "Honkanen", "given": "Jarno", "initials": "J"}, {"family": "Halonen", "given": "Jussi", "initials": "J"}, {"family": "Kuryk", "given": "Lukasz", "initials": "L", "orcid": "0000-0003-1887-6361", "researcher": {"href": "https://publications.scilifelab.se/researcher/cfa535fd845648f5ab10d0e1a407f8f9.json"}}, {"family": "Rescigno", "given": "Maria", "initials": "M", "orcid": "0000-0002-6464-509X", "researcher": {"href": "https://publications.scilifelab.se/researcher/ee52150f5c1c4140aaf8758fff64572c.json"}}, {"family": "Gr\u00f6nholm", "given": "Mikaela", "initials": "M"}, {"family": "Branca", "given": "Rui M", "initials": "RM", "orcid": "0000-0003-3890-6476", "researcher": {"href": "https://publications.scilifelab.se/researcher/87d6256540174d3da581d4572f9d182a.json"}}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Cerullo", "given": "Vincenzo", "initials": "V", "orcid": "0000-0003-4901-3796", "researcher": {"href": "https://publications.scilifelab.se/researcher/6404cf54a990420fb0b63d626aa783fb.json"}}], "type": "journal article", "published": "2023-11-03", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "14", "issue": "1", "pages": "7056", "issn-l": "2041-1723"}, "abstract": "Malignant pleural mesothelioma (MPM) is an aggressive tumor with a poor prognosis. As the available therapeutic options show a lack of efficacy, novel therapeutic strategies are urgently needed. Given its T-cell infiltration, we hypothesized that MPM is a suitable target for therapeutic cancer vaccination. To date, research on mesothelioma has focused on the identification of molecular signatures to better classify and characterize the disease, and little is known about therapeutic targets that engage cytotoxic (CD8+) T cells. In this study we investigate the immunopeptidomic antigen-presented landscape of MPM in both murine (AB12 cell line) and human cell lines (H28, MSTO-211H, H2452, and JL1), as well as in patients' primary tumors. Applying state-of-the-art immuno-affinity purification methodologies, we identify MHC I-restricted peptides presented on the surface of malignant cells. We characterize in vitro the immunogenicity profile of the eluted peptides using T cells from human healthy donors and cancer patients. Furthermore, we use the most promising peptides to formulate an oncolytic virus-based precision immunotherapy (PeptiCRAd) and test its efficacy in a mouse model of mesothelioma in female mice. Overall, we demonstrate that the use of immunopeptidomic analysis in combination with oncolytic immunotherapy represents a feasible and effective strategy to tackle untreatable tumors.", "doi": "10.1038/s41467-023-42668-7", "pmid": "37923723", "labels": {"Global Proteomics and Proteogenomics": "Technology development"}, "xrefs": [{"db": "pmc", "key": "PMC10624665"}, {"db": "pii", "key": "10.1038/s41467-023-42668-7"}], "notes": [], "created": "2023-11-30T10:26:49.610Z", "modified": "2023-11-30T10:26:49.935Z"}, {"entity": "publication", "iuid": "e100499748ca4919a43efecd22554d70", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e100499748ca4919a43efecd22554d70.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e100499748ca4919a43efecd22554d70"}}, "title": "Comprehensive proteomics and meta-analysis of COVID-19 host response.", "authors": [{"family": "Baba\u010di\u0107", "given": "Haris", "initials": "H", "orcid": "0000-0003-0813-0005", "researcher": {"href": "https://publications.scilifelab.se/researcher/45a1c5d3d2d34a9e96d112877632784c.json"}}, {"family": "Christ", "given": "Wanda", "initials": "W", "orcid": "0000-0003-3886-5248", "researcher": {"href": "https://publications.scilifelab.se/researcher/38fe3a44fdb547b885cce5b6f490b2bc.json"}}, {"family": "Ara\u00fajo", "given": "Jos\u00e9 Eduardo", "initials": "JE"}, {"family": "Mermelekas", "given": "Georgios", "initials": "G"}, {"family": "Sharma", "given": "Nidhi", "initials": "N"}, {"family": "Tynell", "given": "Janne", "initials": "J", "orcid": "0000-0001-6930-5230", "researcher": {"href": "https://publications.scilifelab.se/researcher/fb43fb2383e047679010f0969a115f2f.json"}}, {"family": "Garc\u00eda", "given": "Marina", "initials": "M", "orcid": "0000-0002-9130-3933", "researcher": {"href": "https://publications.scilifelab.se/researcher/20fa6d5f40764b32a70f792f29d97e60.json"}}, {"family": "Varnaite", "given": "Renata", "initials": "R"}, {"family": "Asgeirsson", "given": "Hilmir", "initials": "H", "orcid": "0000-0003-3869-8021", "researcher": {"href": "https://publications.scilifelab.se/researcher/dc2be98322a74715a21f56ce31217d84.json"}}, {"family": "Glans", "given": "Hedvig", "initials": "H"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Gredmark-Russ", "given": "Sara", "initials": "S"}, {"family": "Klingstr\u00f6m", "given": "Jonas", "initials": "J", "orcid": "0000-0001-9076-1441", "researcher": {"href": "https://publications.scilifelab.se/researcher/95c1b345ae434fb383b7fe6a1d053c80.json"}}, {"family": "Pernemalm", "given": "Maria", "initials": "M", "orcid": "0000-0003-4624-031X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f15f303cb2044cfa81719700137e3603.json"}}], "type": "meta-analysis", "published": "2023-09-22", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "14", "issue": "1", "pages": "5921", "issn-l": "2041-1723"}, "abstract": "COVID-19 is characterised by systemic immunological perturbations in the human body, which can lead to multi-organ damage. Many of these processes are considered to be mediated by the blood. Therefore, to better understand the systemic host response to SARS-CoV-2 infection, we performed systematic analyses of the circulating, soluble proteins in the blood through global proteomics by mass-spectrometry (MS) proteomics. Here, we show that a large part of the soluble blood proteome is altered in COVID-19, among them elevated levels of interferon-induced and proteasomal proteins. Some proteins that have alternating levels in human cells after a SARS-CoV-2 infection in vitro and in different organs of COVID-19 patients are deregulated in the blood, suggesting shared infection-related changes.The availability of different public proteomic resources on soluble blood proteome alterations leaves uncertainty about the change of a given protein during COVID-19. Hence, we performed a systematic review and meta-analysis of MS global proteomics studies of soluble blood proteomes, including up to 1706 individuals (1039 COVID-19 patients), to provide concluding estimates for the alteration of 1517 soluble blood proteins in COVID-19. Finally, based on the meta-analysis we developed CoViMAPP, an open-access resource for effect sizes of alterations and diagnostic potential of soluble blood proteins in COVID-19, which is publicly available for the research, clinical, and academic community.", "doi": "10.1038/s41467-023-41159-z", "pmid": "37739942", "labels": {"Global Proteomics and Proteogenomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC10516886"}, {"db": "pii", "key": "10.1038/s41467-023-41159-z"}], "notes": [], "created": "2023-11-29T11:54:56.281Z", "modified": "2023-11-29T11:54:56.390Z"}, {"entity": "publication", "iuid": "bc40489e55b44ff3a373a1f1785718d1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/bc40489e55b44ff3a373a1f1785718d1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/bc40489e55b44ff3a373a1f1785718d1"}}, "title": "Proteogenomic analysis of acute myeloid leukemia associates relapsed disease with reprogrammed energy metabolism both in adults and children.", "authors": [{"family": "Stratmann", "given": "Svea", "initials": "S", "orcid": "0000-0002-7438-9093", "researcher": {"href": "https://publications.scilifelab.se/researcher/3927efe3aaf84399b26355d92c3a15cf.json"}}, {"family": "Vesterlund", "given": "Mattias", "initials": "M", "orcid": "0000-0001-9471-6592", "researcher": {"href": "https://publications.scilifelab.se/researcher/0942e438993b494db2a3db914852c808.json"}}, {"family": "Umer", "given": "Husen M", "initials": "HM", "orcid": "0000-0003-3971-2462", "researcher": {"href": "https://publications.scilifelab.se/researcher/db1b83fca3c740f7a20e8dc9f2a1331c.json"}}, {"family": "Eshtad", "given": "Saeed", "initials": "S"}, {"family": "Skaftason", "given": "Aron", "initials": "A"}, {"family": "Herlin", "given": "Morten Krogh", "initials": "MK", "orcid": "0000-0001-7179-4643", "researcher": {"href": "https://publications.scilifelab.se/researcher/fc2efb7b874d46879e3f34e3d7a1b8ef.json"}}, {"family": "Sundstr\u00f6m", "given": "Christer", "initials": "C", "orcid": "0000-0002-8160-5647", "researcher": {"href": "https://publications.scilifelab.se/researcher/dfac750a70664f9986b3cc06334638cc.json"}}, {"family": "Eriksson", "given": "Anna", "initials": "A", "orcid": "0000-0002-8853-1863", "researcher": {"href": "https://publications.scilifelab.se/researcher/53cfc6bb334e455d9f64172ff43e3428.json"}}, {"family": "H\u00f6glund", "given": "Martin", "initials": "M"}, {"family": "Palle", "given": "Josefine", "initials": "J"}, {"family": "Abrahamsson", "given": "Jonas", "initials": "J"}, {"family": "Jahnukainen", "given": "Kirsi", "initials": "K", "orcid": "0000-0001-9296-2028", "researcher": {"href": "https://publications.scilifelab.se/researcher/ec8cc2ae60a245e4807ce50c05273ded.json"}}, {"family": "Munthe-Kaas", "given": "Monica Cheng", "initials": "MC"}, {"family": "Zeller", "given": "Bernward", "initials": "B"}, {"family": "Tamm", "given": "Katja Pokrovskaja", "initials": "KP", "orcid": "0000-0001-6359-1256", "researcher": {"href": "https://publications.scilifelab.se/researcher/09ec3ee706764024bd748c7a77443845.json"}}, {"family": "Lindskog", "given": "Cecilia", "initials": "C"}, {"family": "Cavelier", "given": "Lucia", "initials": "L"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Holmfeldt", "given": "Linda", "initials": "L", "orcid": "0000-0003-4140-3423", "researcher": {"href": "https://publications.scilifelab.se/researcher/12b8b368e61e48d3b800516f006fbb7d.json"}}], "type": "journal article", "published": "2023-03-00", "journal": {"title": "Leukemia", "issn": "1476-5551", "volume": "37", "issue": "3", "pages": "550-559", "issn-l": "0887-6924"}, "abstract": "Despite improvement of current treatment strategies and novel targeted drugs, relapse and treatment resistance largely determine the outcome for acute myeloid leukemia (AML) patients. To identify the underlying molecular characteristics, numerous studies have been aimed to decipher the genomic- and transcriptomic landscape of AML. Nevertheless, further molecular changes allowing malignant cells to escape treatment remain to be elucidated. Mass spectrometry is a powerful tool enabling detailed insights into proteomic changes that could explain AML relapse and resistance. Here, we investigated AML samples from 47 adult and 22 pediatric patients at serial time-points during disease progression using mass spectrometry-based in-depth proteomics. We show that the proteomic profile at relapse is enriched for mitochondrial ribosomal proteins and subunits of the respiratory chain complex, indicative of reprogrammed energy metabolism from diagnosis to relapse. Further, higher levels of granzymes and lower levels of the anti-inflammatory protein CR1/CD35 suggest an inflammatory signature promoting disease progression. Finally, through a proteogenomic approach, we detected novel peptides, which present a promising repertoire in the search for biomarkers and tumor-specific druggable targets. Altogether, this study highlights the importance of proteomic studies in holistic approaches to improve treatment and survival of AML patients.", "doi": "10.1038/s41375-022-01796-7", "pmid": "36572751", "labels": {"Global Proteomics and Proteogenomics": "Collaborative", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9991901"}, {"db": "pii", "key": "10.1038/s41375-022-01796-7"}], "notes": [], "created": "2023-06-07T14:15:49.018Z", "modified": "2024-01-16T13:48:33.897Z"}, {"entity": "publication", "iuid": "c11542cd240549aeb057f59e221c23d1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c11542cd240549aeb057f59e221c23d1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c11542cd240549aeb057f59e221c23d1"}}, "title": "Proteogenomics refines the molecular classification of chronic lymphocytic leukemia", "authors": [{"family": "Herbst", "given": "Sophie A", "initials": "SA", "orcid": "0000-0001-8502-0366", "researcher": {"href": "https://publications.scilifelab.se/researcher/760334e16daa4899b4abbb38f07e7a5f.json"}}, {"family": "Vesterlund", "given": "Mattias", "initials": "M", "orcid": "0000-0001-9471-6592", "researcher": {"href": "https://publications.scilifelab.se/researcher/0942e438993b494db2a3db914852c808.json"}}, {"family": "Helmboldt", "given": "Alexander J", "initials": "AJ", "orcid": "0000-0002-0807-7518", "researcher": {"href": "https://publications.scilifelab.se/researcher/9e7cc6012b6f4ad98bb8767293f676ee.json"}}, {"family": "Jafari", "given": "Rozbeh", "initials": "R", "orcid": "0000-0002-3396-4709", "researcher": {"href": "https://publications.scilifelab.se/researcher/481b2a2329634f9086cf52fb808edea5.json"}}, {"family": "Siavelis", "given": "Ioannis", "initials": "I"}, {"family": "Stahl", "given": "Matthias", "initials": "M", "orcid": "0000-0002-0176-9386", "researcher": {"href": "https://publications.scilifelab.se/researcher/f113f8aa6e77444d9492b5fed0067b25.json"}}, {"family": "Schitter", "given": "Eva C", "initials": "EC"}, {"family": "Liebers", "given": "Nora", "initials": "N"}, {"family": "Brinkmann", "given": "Berit J", "initials": "BJ", "orcid": "0000-0002-0457-2159", "researcher": {"href": "https://publications.scilifelab.se/researcher/ce4155b57a554aa0a105c4245ae265eb.json"}}, {"family": "Czernilofsky", "given": "Felix", "initials": "F", "orcid": "0000-0001-5868-2890", "researcher": {"href": "https://publications.scilifelab.se/researcher/7f8a18192669486b9b05dfc57d453770.json"}}, {"family": "Roider", "given": "Tobias", "initials": "T", "orcid": "0000-0002-6973-3531", "researcher": {"href": "https://publications.scilifelab.se/researcher/b39f6a40851c48a19a3cfb0b20bbcfbd.json"}}, {"family": "Bruch", "given": "Peter Martin", "initials": "PM", "orcid": "0000-0002-9992-3109", "researcher": {"href": "https://publications.scilifelab.se/researcher/01d972f1ca834f4eb0f3a9a949a85f97.json"}}, {"family": "Iskar", "given": "Murat", "initials": "M", "orcid": "0000-0001-8603-4313", "researcher": {"href": "https://publications.scilifelab.se/researcher/a94f83023a4b49488cd5d657604c5b78.json"}}, {"family": "Kittai", "given": "Adam", "initials": "A"}, {"family": "Huang", "given": "Ying", "initials": "Y"}, {"family": "Lu", "given": "Junyan", "initials": "J", "orcid": "0000-0002-9211-0746", "researcher": {"href": "https://publications.scilifelab.se/researcher/08813991edd84a809d5a3e0e0bfaaa2e.json"}}, {"family": "Richter", "given": "Sarah", "initials": "S"}, {"family": "Mermelekas", "given": "Georgios", "initials": "G"}, {"family": "Umer", "given": "Husen Muhammad", "initials": "HM", "orcid": "0000-0003-3971-2462", "researcher": {"href": "https://publications.scilifelab.se/researcher/db1b83fca3c740f7a20e8dc9f2a1331c.json"}}, {"family": "Knoll", "given": "Mareike", "initials": "M"}, {"family": "Kolb", "given": "Carolin", "initials": "C"}, {"family": "Lenze", "given": "Angela", "initials": "A"}, {"family": "Cao", "given": "Xiaofang", "initials": "X"}, {"family": "\u00d6sterholm", "given": "Cecilia", "initials": "C"}, {"family": "Wahnschaffe", "given": "Linus", "initials": "L"}, {"family": "Herling", "given": "Carmen", "initials": "C"}, {"family": "Scheinost", "given": "Sebastian", "initials": "S"}, {"family": "Ganzinger", "given": "Matthias", "initials": "M", "orcid": "0000-0002-2716-5425", "researcher": {"href": "https://publications.scilifelab.se/researcher/73a168f3da3b48adadad47cafd3f3f64.json"}}, {"family": "Mansouri", "given": "Larry", "initials": "L"}, {"family": "Kriegsmann", "given": "Katharina", "initials": "K"}, {"family": "Kriegsmann", "given": "Mark", "initials": "M"}, {"family": "Anders", "given": "Simon", "initials": "S", "orcid": "0000-0003-4868-1805", "researcher": {"href": "https://publications.scilifelab.se/researcher/c11e0cc8bbb846ac821dcd782024c0cc.json"}}, {"family": "Zapatka", "given": "Marc", "initials": "M", "orcid": "0000-0001-8287-5967", "researcher": {"href": "https://publications.scilifelab.se/researcher/0f34c95a849a4a2e8e48dd98034cba88.json"}}, {"family": "Del Poeta", "given": "Giovanni", "initials": "G"}, {"family": "Zucchetto", "given": "Antonella", "initials": "A"}, {"family": "Bomben", "given": "Riccardo", "initials": "R", "orcid": "0000-0002-8746-9404", "researcher": {"href": "https://publications.scilifelab.se/researcher/72fc218ceb84460ca0eece578e06593e.json"}}, {"family": "Gattei", "given": "Valter", "initials": "V", "orcid": "0000-0001-5933-9680", "researcher": {"href": "https://publications.scilifelab.se/researcher/e2d6143330194f1d99705b0d60808f74.json"}}, {"family": "Dreger", "given": "Peter", "initials": "P"}, {"family": "Woyach", "given": "Jennifer", "initials": "J", "orcid": "0000-0002-3403-9144", "researcher": {"href": "https://publications.scilifelab.se/researcher/cd77b10bbd084fed98ab2f647a247bf3.json"}}, {"family": "Herling", "given": "Marco", "initials": "M"}, {"family": "M\u00fcller-Tidow", "given": "Carsten", "initials": "C", "orcid": "0000-0002-7166-5232", "researcher": {"href": "https://publications.scilifelab.se/researcher/16f6edb14cb74bbdb221ea2ae0e1ab27.json"}}, {"family": "Rosenquist", "given": "Richard", "initials": "R", "orcid": "0000-0002-0211-8788", "researcher": {"href": "https://publications.scilifelab.se/researcher/b570128e641140fb964ae3241414f510.json"}}, {"family": "Stilgenbauer", "given": "Stephan", "initials": "S"}, {"family": "Zenz", "given": "Thorsten", "initials": "T", "orcid": "0000-0001-7890-9845", "researcher": {"href": "https://publications.scilifelab.se/researcher/8f6b107b1ec94de7bbc260f92f2dcc9f.json"}}, {"family": "Huber", "given": "Wolfgang", "initials": "W", "orcid": "0000-0002-0474-2218", "researcher": {"href": "https://publications.scilifelab.se/researcher/4dacd52a252743b09b7f7383b95aaf36.json"}}, {"family": "Tausch", "given": "Eugen", "initials": "E"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Dietrich", "given": "Sascha", "initials": "S", "orcid": "0000-0002-0648-1832", "researcher": {"href": "https://publications.scilifelab.se/researcher/7ddfd067d9b34285bd51eb0c08f4b73f.json"}}], "type": "journal-article", "published": "2022-10-20", "journal": {"title": "Nat Commun", "issn": "2041-1723", "issn-l": "2041-1723", "volume": "13", "issue": "1", "pages": "6226"}, "abstract": "Cancer heterogeneity at the proteome level may explain differences in therapy response and prognosis beyond the currently established genomic and transcriptomic-based diagnostics. The relevance of proteomics for disease classifications remains to be established in clinically heterogeneous cancer entities such as chronic lymphocytic leukemia (CLL). Here, we characterize the proteome and transcriptome alongside genetic and ex-vivo drug response profiling in a clinically annotated CLL discovery cohort (n = 68). Unsupervised clustering of the proteome data reveals six subgroups. Five of these proteomic groups are associated with genetic features, while one group is only detectable at the proteome level. This new group is characterized by accelerated disease progression, high spliceosomal protein abundances associated with aberrant splicing, and low B cell receptor signaling protein abundances (ASB-CLL). Classifiers developed to identify ASB-CLL based on its characteristic proteome or splicing signature in two independent cohorts (n = 165, n = 169) confirm that ASB-CLL comprises about 20% of CLL patients. The inferior overall survival in ASB-CLL is also independent of both TP53- and IGHV mutation status. Our multi-omics analysis refines the classification of CLL and highlights the potential of proteomics to improve cancer patient stratification beyond genetic and transcriptomic profiling.", "doi": "10.1038/s41467-022-33385-8", "pmid": "36266272", "labels": {"Global Proteomics and Proteogenomics": "Technology development"}, "xrefs": [{"db": "pmc", "key": "PMC9584885"}, {"db": "pii", "key": "10.1038/s41467-022-33385-8"}], "notes": [], "created": "2023-06-07T14:08:49.429Z", "modified": "2023-06-19T10:57:58.320Z"}, {"entity": "publication", "iuid": "2d0a1e4f50174086a1d35a8e989e39b7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2d0a1e4f50174086a1d35a8e989e39b7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2d0a1e4f50174086a1d35a8e989e39b7"}}, "title": "SubCellBarCode: integrated workflow for robust spatial proteomics by mass spectrometry.", "authors": [{"family": "Arslan", "given": "Taner", "initials": "T", "orcid": "0000-0002-2388-1811", "researcher": {"href": "https://publications.scilifelab.se/researcher/058646e344cd49b18da884284ea08355.json"}}, {"family": "Pan", "given": "Yanbo", "initials": "Y", "orcid": "0000-0001-9442-7782", "researcher": {"href": "https://publications.scilifelab.se/researcher/00403ea0d7bd4218a6b9ba507fa2fa26.json"}}, {"family": "Mermelekas", "given": "Georgios", "initials": "G"}, {"family": "Vesterlund", "given": "Mattias", "initials": "M", "orcid": "0000-0001-9471-6592", "researcher": {"href": "https://publications.scilifelab.se/researcher/0942e438993b494db2a3db914852c808.json"}}, {"family": "Orre", "given": "Lukas M", "initials": "LM"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}], "type": "journal article", "published": "2022-08-00", "journal": {"title": "Nat Protoc", "issn": "1750-2799", "volume": "17", "issue": "8", "pages": "1832-1867", "issn-l": null}, "abstract": "The molecular functions of a protein are defined by its inherent properties in relation to its environment and interaction network. Within a cell, this environment and network are defined by the subcellular location of the protein. Consequently, it is crucial to know the localization of a protein to fully understand its functions. Recently, we have developed a mass spectrometry- (MS) and bioinformatics-based pipeline to generate a proteome-wide resource for protein subcellular localization across multiple human cancer cell lines ( www.subcellbarcode.org ). Here, we present a detailed wet-lab protocol spanning from subcellular fractionation to MS-sample preparation and analysis. A key feature of this protocol is that it includes all generated cell fractions without discarding any material during the fractionation process. We also describe the subsequent quantitative MS-data analysis, machine learning-based classification, differential localization analysis and visualization of the output. For broad applicability, we evaluated the pipeline by using MS data generated by two different peptide pre-fractionation approaches, namely high-resolution isoelectric focusing and high-pH reverse-phase fractionation, as well as direct analysis without pre-fractionation by using long-gradient liquid chromatography-MS. Moreover, an R package covering the dry-lab part of the method was developed and made available through Bioconductor. The method is straightforward and robust, and the entire protocol, from cell harvest to classification output, can be performed within 1-2 weeks. The protocol enables accurate classification of proteins to 15 compartments and 4 neighborhoods, visualization of the output data and differential localization analysis including treatment-induced protein relocalization, condition-dependent localization or cell type-specific localization. The SubCellBarCode package is freely available at https://bioconductor.org/packages/devel/bioc/html/SubCellBarCode.html .", "doi": "10.1038/s41596-022-00699-2", "pmid": "35732783", "labels": {"Global Proteomics and Proteogenomics": "Technology development"}, "xrefs": [{"db": "pii", "key": "10.1038/s41596-022-00699-2"}], "notes": [], "created": "2022-11-24T08:32:26.083Z", "modified": "2023-11-29T12:03:56.113Z"}, {"entity": "publication", "iuid": "1a1d9f2b8c78456e97322487cf985e6d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1a1d9f2b8c78456e97322487cf985e6d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1a1d9f2b8c78456e97322487cf985e6d"}}, "title": "Author Correction: The Molecular Tumor Board Portal supports clinical decisions and automated reporting for precision oncology.", "authors": [{"family": "Tamborero", "given": "David", "initials": "D", "orcid": "0000-0002-7218-2806", "researcher": {"href": "https://publications.scilifelab.se/researcher/740d488afc204156b682b67589992023.json"}}, {"family": "Dienstmann", "given": "Rodrigo", "initials": "R"}, {"family": "Rachid", "given": "Maan Haj", "initials": "MH"}, {"family": "Boekel", "given": "Jorrit", "initials": "J"}, {"family": "Lopez-Fernandez", "given": "Adria", "initials": "A", "orcid": "0000-0002-2844-5998", "researcher": {"href": "https://publications.scilifelab.se/researcher/959015b1815647edaee690c9d59b1913.json"}}, {"family": "Jonsson", "given": "Markus", "initials": "M"}, {"family": "Razzak", "given": "Ali", "initials": "A"}, {"family": "Bra\u00f1a", "given": "Irene", "initials": "I"}, {"family": "De Petris", "given": "Luigi", "initials": "L"}, {"family": "Yachnin", "given": "Jeffrey", "initials": "J"}, {"family": "Baird", "given": "Richard D", "initials": "RD", "orcid": "0000-0001-7071-6483", "researcher": {"href": "https://publications.scilifelab.se/researcher/11aa354bf2f74c4d8c31f3e0faf650db.json"}}, {"family": "Loriot", "given": "Yohann", "initials": "Y"}, {"family": "Massard", "given": "Christophe", "initials": "C"}, {"family": "Martin-Romano", "given": "Patricia", "initials": "P"}, {"family": "Opdam", "given": "Frans", "initials": "F"}, {"family": "Schlenk", "given": "Richard F", "initials": "RF"}, {"family": "Vernieri", "given": "Claudio", "initials": "C"}, {"family": "Masucci", "given": "Michele", "initials": "M"}, {"family": "Villalobos", "given": "Xenia", "initials": "X"}, {"family": "Chavarria", "given": "Elena", "initials": "E"}, {"family": "Cancer Core Europe consortium", "given": "", "initials": ""}, {"family": "Balma\u00f1a", "given": "Judith", "initials": "J", "orcid": "0000-0002-0762-6415", "researcher": {"href": "https://publications.scilifelab.se/researcher/3bd06da8f9fa4d56bdc176d31695f78f.json"}}, {"family": "Apolone", "given": "Giovanni", "initials": "G"}, {"family": "Caldas", "given": "Carlos", "initials": "C", "orcid": "0000-0003-3547-1489", "researcher": {"href": "https://publications.scilifelab.se/researcher/0cc09ee06f6c4391ba062ac65e85cb55.json"}}, {"family": "Bergh", "given": "Jonas", "initials": "J", "orcid": "0000-0001-5526-1847", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd38f4f7704144ed9e3f869e197175e6.json"}}, {"family": "Ernberg", "given": "Ingemar", "initials": "I", "orcid": "0000-0001-6518-1648", "researcher": {"href": "https://publications.scilifelab.se/researcher/1da842a1d09c4268840407774e351809.json"}}, {"family": "Fr\u00f6hling", "given": "Stefan", "initials": "S", "orcid": "0000-0001-7907-4595", "researcher": {"href": "https://publications.scilifelab.se/researcher/cd46d3f4c2084ce7922ceb0220b09277.json"}}, {"family": "Garralda", "given": "Elena", "initials": "E"}, {"family": "Karlsson", "given": "Claes", "initials": "C"}, {"family": "Tabernero", "given": "Josep", "initials": "J", "orcid": "0000-0002-2495-8139", "researcher": {"href": "https://publications.scilifelab.se/researcher/c9be0e16fc3f415e92754a6135bfc164.json"}}, {"family": "Voest", "given": "Emile", "initials": "E", "orcid": "0000-0001-8249-9586", "researcher": {"href": "https://publications.scilifelab.se/researcher/e5a8340e3b0445bea291f971e1c2c75e.json"}}, {"family": "Rodon", "given": "Jordi", "initials": "J"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}], "type": "published erratum", "published": "2022-05-00", "journal": {"title": "Nat Cancer", "issn": "2662-1347", "volume": "3", "issue": "5", "pages": "649", "issn-l": null}, "abstract": null, "doi": "10.1038/s43018-022-00378-x", "pmid": "35449310", "labels": {"Global Proteomics and Proteogenomics": "Technology development"}, "xrefs": [{"db": "pmc", "key": "PMC9135626"}, {"db": "pii", "key": "10.1038/s43018-022-00378-x"}], "notes": [], "created": "2022-11-24T20:27:37.980Z", "modified": "2022-11-25T19:50:36.186Z"}, {"entity": "publication", "iuid": "9ebcad7df6fc4b52a1198f4a36faeb0e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9ebcad7df6fc4b52a1198f4a36faeb0e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9ebcad7df6fc4b52a1198f4a36faeb0e"}}, "title": "Integrative multi-omics and drug response profiling of childhood acute lymphoblastic leukemia cell lines.", "authors": [{"family": "Leo", "given": "Isabelle Rose", "initials": "IR", "orcid": "0000-0002-7627-6690", "researcher": {"href": "https://publications.scilifelab.se/researcher/21185d9c6a2343f189397cbbb95c6e71.json"}}, {"family": "Aswad", "given": "Luay", "initials": "L", "orcid": "0000-0002-8730-9208", "researcher": {"href": "https://publications.scilifelab.se/researcher/f01cefe048a541c7bdab2727d9cfc79d.json"}}, {"family": "Stahl", "given": "Matthias", "initials": "M", "orcid": "0000-0002-0176-9386", "researcher": {"href": "https://publications.scilifelab.se/researcher/f113f8aa6e77444d9492b5fed0067b25.json"}}, {"family": "Kunold", "given": "Elena", "initials": "E"}, {"family": "Post", "given": "Frederik", "initials": "F", "orcid": "0000-0003-0376-1326", "researcher": {"href": "https://publications.scilifelab.se/researcher/439eb72d3314446da93915e854774caf.json"}}, {"family": "Erkers", "given": "Tom", "initials": "T"}, {"family": "Struyf", "given": "Nona", "initials": "N", "orcid": "0000-0002-6975-0753", "researcher": {"href": "https://publications.scilifelab.se/researcher/1295c3be31024c4fa2da10cffe42c406.json"}}, {"family": "Mermelekas", "given": "Georgios", "initials": "G"}, {"family": "Joshi", "given": "Rubin Narayan", "initials": "RN"}, {"family": "Gracia-Villacampa", "given": "Eva", "initials": "E", "orcid": "0000-0003-0353-2101", "researcher": {"href": "https://publications.scilifelab.se/researcher/eaf72d81feea4b7899197c67131a85ba.json"}}, {"family": "\u00d6stling", "given": "P\u00e4ivi", "initials": "P"}, {"family": "Kallioniemi", "given": "Olli P", "initials": "OP"}, {"family": "Tamm", "given": "Katja Pokrovskaja", "initials": "KP", "orcid": "0000-0001-6359-1256", "researcher": {"href": "https://publications.scilifelab.se/researcher/09ec3ee706764024bd748c7a77443845.json"}}, {"family": "Siavelis", "given": "Ioannis", "initials": "I"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Vesterlund", "given": "Mattias", "initials": "M", "orcid": "0000-0001-9471-6592", "researcher": {"href": "https://publications.scilifelab.se/researcher/0942e438993b494db2a3db914852c808.json"}}, {"family": "Jafari", "given": "Rozbeh", "initials": "R", "orcid": "0000-0002-3396-4709", "researcher": {"href": "https://publications.scilifelab.se/researcher/481b2a2329634f9086cf52fb808edea5.json"}}], "type": "journal article", "published": "2022-03-30", "journal": {"title": "Nat Commun", "issn": "2041-1723", "issn-l": "2041-1723", "volume": "13", "issue": "1", "pages": "1691"}, "abstract": "Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Although standard-of-care chemotherapeutics are sufficient for most ALL cases, there are subsets of patients with poor response who relapse in disease. The biology underlying differences between subtypes and their response to therapy has only partially been explained by genetic and transcriptomic profiling. Here, we perform comprehensive multi-omic analyses of 49 readily available childhood ALL cell lines, using proteomics, transcriptomics, and pharmacoproteomic characterization. We connect the molecular phenotypes with drug responses to 528 oncology drugs, identifying drug correlations as well as lineage-dependent correlations. We also identify the diacylglycerol-analog bryostatin-1 as a therapeutic candidate in the MEF2D-HNRNPUL1 fusion high-risk subtype, for which this drug activates pro-apoptotic ERK signaling associated with molecular mediators of pre-B cell negative selection. Our data is the foundation for the interactive online Functional Omics Resource of ALL (FORALL) with navigable proteomics, transcriptomics, and drug sensitivity profiles at https://proteomics.se/forall .", "doi": "10.1038/s41467-022-29224-5", "pmid": "35354797", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Production)": "Service", "NGI Short read": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8967900"}, {"db": "pii", "key": "10.1038/s41467-022-29224-5"}], "notes": [], "created": "2022-08-19T08:37:13.488Z", "modified": "2024-01-16T13:48:37.216Z"}, {"entity": "publication", "iuid": "5aa5cb6b38054618b069b6961ae1f580", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5aa5cb6b38054618b069b6961ae1f580.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5aa5cb6b38054618b069b6961ae1f580"}}, "title": "A novel immunopeptidomic-based pipeline for the generation of personalized oncolytic cancer vaccines.", "authors": [{"family": "Feola", "given": "Sara", "initials": "S", "orcid": "0000-0002-4012-4310", "researcher": {"href": "https://publications.scilifelab.se/researcher/c9d2c4168aa541b5ad9a7e5155dc1069.json"}}, {"family": "Chiaro", "given": "Jacopo", "initials": "J"}, {"family": "Martins", "given": "Beatriz", "initials": "B"}, {"family": "Russo", "given": "Salvatore", "initials": "S"}, {"family": "Fusciello", "given": "Manlio", "initials": "M"}, {"family": "Yl\u00f6sm\u00e4ki", "given": "Erkko", "initials": "E"}, {"family": "Bonini", "given": "Chiara", "initials": "C"}, {"family": "Ruggiero", "given": "Eliana", "initials": "E"}, {"family": "Hamdan", "given": "Firas", "initials": "F"}, {"family": "Feodoroff", "given": "Michaela", "initials": "M", "orcid": "0000-0002-6094-9838", "researcher": {"href": "https://publications.scilifelab.se/researcher/b828ef2f6621496cbc6ac77cc8413c14.json"}}, {"family": "Antignani", "given": "Gabriella", "initials": "G"}, {"family": "Viitala", "given": "Tapani", "initials": "T", "orcid": "0000-0001-9074-9450", "researcher": {"href": "https://publications.scilifelab.se/researcher/9ee6b76dabd84478980890145b47a08a.json"}}, {"family": "Pesonen", "given": "Sari", "initials": "S"}, {"family": "Gr\u00f6nholm", "given": "Mikaela", "initials": "M"}, {"family": "Branca", "given": "Rui M M", "initials": "RMM"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Cerullo", "given": "Vincenzo", "initials": "V", "orcid": "0000-0003-4901-3796", "researcher": {"href": "https://publications.scilifelab.se/researcher/6404cf54a990420fb0b63d626aa783fb.json"}}], "type": "journal article", "published": "2022-03-22", "journal": {"title": "Elife", "issn": "2050-084X", "volume": "11", "issn-l": "2050-084X"}, "abstract": "Besides the isolation and identification of major histocompatibility complex I-restricted peptides from the surface of cancer cells, one of the challenges is eliciting an effective antitumor CD8+ T-cell-mediated response as part of therapeutic cancer vaccine. Therefore, the establishment of a solid pipeline for the downstream selection of clinically relevant peptides and the subsequent creation of therapeutic cancer vaccines are of utmost importance. Indeed, the use of peptides for eliciting specific antitumor adaptive immunity is hindered by two main limitations: the efficient selection of the most optimal candidate peptides and the use of a highly immunogenic platform to combine with the peptides to induce effective tumor-specific adaptive immune responses. Here, we describe for the first time a streamlined pipeline for the generation of personalized cancer vaccines starting from the isolation and selection of the most immunogenic peptide candidates expressed on the tumor cells and ending in the generation of efficient therapeutic oncolytic cancer vaccines. This immunopeptidomics-based pipeline was carefully validated in a murine colon tumor model CT26. Specifically, we used state-of-the-art immunoprecipitation and mass spectrometric methodologies to isolate >8000 peptide targets from the CT26 tumor cell line. The selection of the target candidates was then based on two separate approaches: RNAseq analysis and HEX software. The latter is a tool previously developed by Jacopo, 2020, able to identify tumor antigens similar to pathogen antigens in order to exploit molecular mimicry and tumor pathogen cross-reactive T cells in cancer vaccine development. The generated list of candidates (26 in total) was further tested in a functional characterization assay using interferon-\u03b3 enzyme-linked immunospot (ELISpot), reducing the number of candidates to six. These peptides were then tested in our previously described oncolytic cancer vaccine platform PeptiCRAd, a vaccine platform that combines an immunogenic oncolytic adenovirus (OAd) coated with tumor antigen peptides. In our work, PeptiCRAd was successfully used for the treatment of mice bearing CT26, controlling the primary malignant lesion and most importantly a secondary, nontreated, cancer lesion. These results confirmed the feasibility of applying the described pipeline for the selection of peptide candidates and generation of therapeutic oncolytic cancer vaccine, filling a gap in the field of cancer immunotherapy, and paving the way to translate our pipeline into human therapeutic approach.", "doi": "10.7554/eLife.71156", "pmid": "35314027", "labels": {"Global Proteomics and Proteogenomics": "Technology development"}, "xrefs": [{"db": "pmc", "key": "PMC8989416"}, {"db": "pii", "key": "71156"}, {"db": "GEO", "key": "GSE111092"}, {"db": "GEO", "key": "GSE92563"}], "notes": [], "created": "2022-11-24T08:28:27.553Z", "modified": "2022-11-24T08:28:27.759Z"}, {"entity": "publication", "iuid": "2bcf23149f1f428991a34f8da5396b04", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2bcf23149f1f428991a34f8da5396b04.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2bcf23149f1f428991a34f8da5396b04"}}, "title": "The Molecular Tumor Board Portal supports clinical decisions and automated reporting for precision oncology.", "authors": [{"family": "Tamborero", "given": "David", "initials": "D", "orcid": "0000-0002-7218-2806", "researcher": {"href": "https://publications.scilifelab.se/researcher/740d488afc204156b682b67589992023.json"}}, {"family": "Dienstmann", "given": "Rodrigo", "initials": "R"}, {"family": "Rachid", "given": "Maan Haj", "initials": "MH"}, {"family": "Boekel", "given": "Jorrit", "initials": "J"}, {"family": "Lopez-Fernandez", "given": "Adria", "initials": "A", "orcid": "0000-0002-2844-5998", "researcher": {"href": "https://publications.scilifelab.se/researcher/959015b1815647edaee690c9d59b1913.json"}}, {"family": "Jonsson", "given": "Markus", "initials": "M"}, {"family": "Razzak", "given": "Ali", "initials": "A"}, {"family": "Bra\u00f1a", "given": "Irene", "initials": "I"}, {"family": "De Petris", "given": "Luigi", "initials": "L"}, {"family": "Yachnin", "given": "Jeffrey", "initials": "J"}, {"family": "Baird", "given": "Richard D", "initials": "RD", "orcid": "0000-0001-7071-6483", "researcher": {"href": "https://publications.scilifelab.se/researcher/11aa354bf2f74c4d8c31f3e0faf650db.json"}}, {"family": "Loriot", "given": "Yohann", "initials": "Y"}, {"family": "Massard", "given": "Christophe", "initials": "C"}, {"family": "Martin-Romano", "given": "Patricia", "initials": "P"}, {"family": "Opdam", "given": "Frans", "initials": "F"}, {"family": "Schlenk", "given": "Richard F", "initials": "RF"}, {"family": "Vernieri", "given": "Claudio", "initials": "C"}, {"family": "Masucci", "given": "Michele", "initials": "M"}, {"family": "Villalobos", "given": "Xenia", "initials": "X"}, {"family": "Chavarria", "given": "Elena", "initials": "E"}, {"family": "Cancer Core Europe consortium", "given": "", "initials": ""}, {"family": "Balma\u00f1a", "given": "Judith", "initials": "J", "orcid": "0000-0002-0762-6415", "researcher": {"href": "https://publications.scilifelab.se/researcher/3bd06da8f9fa4d56bdc176d31695f78f.json"}}, {"family": "Apolone", "given": "Giovanni", "initials": "G"}, {"family": "Caldas", "given": "Carlos", "initials": "C", "orcid": "0000-0003-3547-1489", "researcher": {"href": "https://publications.scilifelab.se/researcher/0cc09ee06f6c4391ba062ac65e85cb55.json"}}, {"family": "Bergh", "given": "Jonas", "initials": "J", "orcid": "0000-0001-5526-1847", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd38f4f7704144ed9e3f869e197175e6.json"}}, {"family": "Ernberg", "given": "Ingemar", "initials": "I", "orcid": "0000-0001-6518-1648", "researcher": {"href": "https://publications.scilifelab.se/researcher/1da842a1d09c4268840407774e351809.json"}}, {"family": "Fr\u00f6hling", "given": "Stefan", "initials": "S", "orcid": "0000-0001-7907-4595", "researcher": {"href": "https://publications.scilifelab.se/researcher/cd46d3f4c2084ce7922ceb0220b09277.json"}}, {"family": "Garralda", "given": "Elena", "initials": "E"}, {"family": "Karlsson", "given": "Claes", "initials": "C"}, {"family": "Tabernero", "given": "Josep", "initials": "J", "orcid": "0000-0002-2495-8139", "researcher": {"href": "https://publications.scilifelab.se/researcher/c9be0e16fc3f415e92754a6135bfc164.json"}}, {"family": "Voest", "given": "Emile", "initials": "E", "orcid": "0000-0001-8249-9586", "researcher": {"href": "https://publications.scilifelab.se/researcher/e5a8340e3b0445bea291f971e1c2c75e.json"}}, {"family": "Rodon", "given": "Jordi", "initials": "J"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}], "type": "journal article", "published": "2022-02-00", "journal": {"title": "Nat Cancer", "issn": "2662-1347", "volume": "3", "issue": "2", "pages": "251-261", "issn-l": null}, "abstract": "There is a growing need for systems that efficiently support the work of medical teams at the precision-oncology point of care. Here, we present the implementation of the Molecular Tumor Board Portal (MTBP), an academic clinical decision support system developed under the umbrella of Cancer Core Europe that creates a unified legal, scientific and technological platform to share and harness next-generation sequencing data. Automating the interpretation and reporting of sequencing results decrease the need for time-consuming manual procedures that are prone to errors. The adoption of an expert-agreed process to systematically link tumor molecular profiles with clinical actions promotes consistent decision-making and structured data capture across the connected centers. The use of information-rich patient reports with interactive content facilitates collaborative discussion of complex cases during virtual molecular tumor board meetings. Overall, streamlined digital systems like the MTBP are crucial to better address the challenges brought by precision oncology and accelerate the use of emerging biomarkers.", "doi": "10.1038/s43018-022-00332-x", "pmid": "35221333", "labels": {"Global Proteomics and Proteogenomics": "Technology development"}, "xrefs": [{"db": "pmc", "key": "PMC8882467"}, {"db": "pii", "key": "10.1038/s43018-022-00332-x"}], "notes": [], "created": "2022-11-25T19:59:26.171Z", "modified": "2022-11-25T19:59:26.239Z"}, {"entity": "publication", "iuid": "ccd54446c7604b2d944e433c3fc245ab", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ccd54446c7604b2d944e433c3fc245ab.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ccd54446c7604b2d944e433c3fc245ab"}}, "title": "Subcellular proteomics.", "authors": [{"family": "Christopher", "given": "Josie A", "initials": "JA"}, {"family": "Stadler", "given": "Charlotte", "initials": "C", "orcid": "0000-0002-6781-1938", "researcher": {"href": "https://publications.scilifelab.se/researcher/2db3b27c7d7143cbacc8c1dd8ac90a31.json"}}, {"family": "Martin", "given": "Claire E", "initials": "CE", "orcid": "0000-0001-8346-414X", "researcher": {"href": "https://publications.scilifelab.se/researcher/283b9e3574454cd6892ab5bc964f7353.json"}}, {"family": "Morgenstern", "given": "Marcel", "initials": "M", "orcid": "0000-0001-6880-4839", "researcher": {"href": "https://publications.scilifelab.se/researcher/8da72791863f463cad99442103d83338.json"}}, {"family": "Pan", "given": "Yanbo", "initials": "Y", "orcid": "0000-0001-9442-7782", "researcher": {"href": "https://publications.scilifelab.se/researcher/00403ea0d7bd4218a6b9ba507fa2fa26.json"}}, {"family": "Betsinger", "given": "Cora N", "initials": "CN", "orcid": "0000-0001-9263-3873", "researcher": {"href": "https://publications.scilifelab.se/researcher/90fe36ad250546f7af5422c53e1aff77.json"}}, {"family": "Rattray", "given": "David G", "initials": "DG", "orcid": "0000-0002-2444-0663", "researcher": {"href": "https://publications.scilifelab.se/researcher/090cec60bc574c29809b7124d80b6170.json"}}, {"family": "Mahdessian", "given": "Diana", "initials": "D", "orcid": "0000-0003-0750-1070", "researcher": {"href": "https://publications.scilifelab.se/researcher/dc22f13eb21a4c75a6e7cad7686bcc8a.json"}}, {"family": "Gingras", "given": "Anne-Claude", "initials": "A", "orcid": "0000-0002-6090-4437", "researcher": {"href": "https://publications.scilifelab.se/researcher/21315bcb23a144069b3568d7afd0b00b.json"}}, {"family": "Warscheid", "given": "Bettina", "initials": "B", "orcid": "0000-0001-5096-1975", "researcher": {"href": "https://publications.scilifelab.se/researcher/24f95112121a4e0c88c746703712017c.json"}}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Cristea", "given": "Ileana M", "initials": "IM"}, {"family": "Foster", "given": "Leonard J", "initials": "LJ", "orcid": "0000-0001-8551-4817", "researcher": {"href": "https://publications.scilifelab.se/researcher/84bc1af03ee243ca91c3f230ce711154.json"}}, {"family": "Emili", "given": "Andrew", "initials": "A", "orcid": "0000-0001-8995-246X", "researcher": {"href": "https://publications.scilifelab.se/researcher/337c75cec31e4051b979e7217d823999.json"}}, {"family": "Lilley", "given": "Kathryn S", "initials": "KS", "orcid": "0000-0003-0594-6543", "researcher": {"href": "https://publications.scilifelab.se/researcher/77b4e7e18a88455199308070d6da7ea3.json"}}], "type": "journal article", "published": "2021-04-29", "journal": {"title": "Nat Rev Methods Primers", "issn": "2662-8449", "issn-l": null, "volume": "1", "issue": "1", "pages": null}, "abstract": "The eukaryotic cell is compartmentalized into subcellular niches, including membrane-bound and membrane-less organelles. Proteins localize to these niches to fulfil their function, enabling discreet biological processes to occur in synchrony. Dynamic movement of proteins between niches is essential for cellular processes such as signalling, growth, proliferation, motility and programmed cell death, and mutations causing aberrant protein localization are associated with a wide range of diseases. Determining the location of proteins in different cell states and cell types and how proteins relocalize following perturbation is important for understanding their functions, related cellular processes and pathologies associated with their mislocalization. In this Primer, we cover the major spatial proteomics methods for determining the location, distribution and abundance of proteins within subcellular structures. These technologies include fluorescent imaging, protein proximity labelling, organelle purification and cell-wide biochemical fractionation. We describe their workflows, data outputs and applications in exploring different cell biological scenarios, and discuss their main limitations. Finally, we describe emerging technologies and identify areas that require technological innovation to allow better characterization of the spatial proteome.", "doi": "10.1038/s43586-021-00029-y", "pmid": "34549195", "labels": {"Spatial Proteomics": "Technology development"}, "xrefs": [{"db": "pmc", "key": "PMC8451152"}, {"db": "mid", "key": "NIHMS1715590"}], "notes": [], "created": "2021-05-04T13:33:02.777Z", "modified": "2023-06-19T11:25:03.018Z"}, {"entity": "publication", "iuid": "da3db1a72f4e4da0b4f59eb56f60145a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/da3db1a72f4e4da0b4f59eb56f60145a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/da3db1a72f4e4da0b4f59eb56f60145a"}}, "title": "Novel Broad-Spectrum Antiviral Inhibitors Targeting Host Factors Essential for Replication of Pathogenic RNA Viruses.", "authors": [{"family": "Tampere", "given": "Marianna", "initials": "M", "orcid": "0000-0001-5744-3206", "researcher": {"href": "https://publications.scilifelab.se/researcher/0c6c86cb20394d17abebb40db23407c8.json"}}, {"family": "Pettke", "given": "Aleksandra", "initials": "A", "orcid": "0000-0001-9375-7755", "researcher": {"href": "https://publications.scilifelab.se/researcher/350bf45edaf64ce1a54b5bb9c27883b5.json"}}, {"family": "Salata", "given": "Cristiano", "initials": "C", "orcid": "0000-0002-5136-7406", "researcher": {"href": "https://publications.scilifelab.se/researcher/0f9a987cf801433ea29960dc97e7fc4d.json"}}, {"family": "Wallner", "given": "Olov", "initials": "O", "orcid": "0000-0002-6481-237X", "researcher": {"href": "https://publications.scilifelab.se/researcher/83eb2f7ee2f34f2cbacaae2dadcd90e9.json"}}, {"family": "Koolmeister", "given": "Tobias", "initials": "T"}, {"family": "Cazares-K\u00f6rner", "given": "Armando", "initials": "A"}, {"family": "Visnes", "given": "Torkild", "initials": "T"}, {"family": "Hesselman", "given": "Maria Carmen", "initials": "MC", "orcid": "0000-0003-4858-6920", "researcher": {"href": "https://publications.scilifelab.se/researcher/c71bbdf11342400ca9031f17a8adca47.json"}}, {"family": "Kunold", "given": "Elena", "initials": "E"}, {"family": "Wiita", "given": "Elisee", "initials": "E"}, {"family": "Kalder\u00e9n", "given": "Christina", "initials": "C"}, {"family": "Lightowler", "given": "Molly", "initials": "M"}, {"family": "Jemth", "given": "Ann-Sofie", "initials": "AS"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Rosenquist", "given": "\u00c5sa", "initials": "\u00c5"}, {"family": "Warpman-Berglund", "given": "Ulrika", "initials": "U"}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7256c271ea4adea404d4ff355f804e.json"}}, {"family": "Mirazimi", "given": "Ali", "initials": "A"}, {"family": "Jafari", "given": "Rozbeh", "initials": "R", "orcid": "0000-0002-3396-4709", "researcher": {"href": "https://publications.scilifelab.se/researcher/481b2a2329634f9086cf52fb808edea5.json"}}, {"family": "Puumalainen", "given": "Marjo-Riitta", "initials": "MR", "orcid": "0000-0002-9936-9734", "researcher": {"href": "https://publications.scilifelab.se/researcher/ffeffbd97cbb4feb9f85e26b368d9f05.json"}}], "type": "journal article", "published": "2020-12-10", "journal": {"title": "Viruses", "issn": "1999-4915", "volume": "12", "issue": "12", "pages": "1423", "issn-l": "1999-4915"}, "abstract": "Recent RNA virus outbreaks such as Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Ebola virus (EBOV) have caused worldwide health emergencies highlighting the urgent need for new antiviral strategies. Targeting host cell pathways supporting viral replication is an attractive approach for development of antiviral compounds, especially with new, unexplored viruses where knowledge of virus biology is limited. Here, we present a strategy to identify host-targeted small molecule inhibitors using an image-based phenotypic antiviral screening assay followed by extensive target identification efforts revealing altered cellular pathways upon antiviral compound treatment. The newly discovered antiviral compounds showed broad-range antiviral activity against pathogenic RNA viruses such as SARS-CoV-2, EBOV and Crimean-Congo hemorrhagic fever virus (CCHFV). Target identification of the antiviral compounds by thermal protein profiling revealed major effects on proteostasis pathways and disturbance in interactions between cellular HSP70 complex and viral proteins, illustrating the supportive role of HSP70 on many RNA viruses across virus families. Collectively, this strategy identifies new small molecule inhibitors with broad antiviral activity against pathogenic RNA viruses, but also uncovers novel virus biology urgently needed for design of new antiviral therapies.", "doi": "10.3390/v12121423", "pmid": "33322045", "labels": {"Global Proteomics and Proteogenomics": "Service"}, "xrefs": [{"db": "pii", "key": "v12121423"}, {"db": "pmc", "key": "PMC7762994"}], "notes": [], "created": "2021-01-12T18:16:58.814Z", "modified": "2022-03-29T11:28:16.687Z"}, {"entity": "publication", "iuid": "aad98531594443b3bdf72d5748622b1e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/aad98531594443b3bdf72d5748622b1e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/aad98531594443b3bdf72d5748622b1e"}}, "title": "Combined transcriptome and proteome profiling of the pancreatic \u03b2-cell response to palmitate unveils key pathways of \u03b2-cell lipotoxicity.", "authors": [{"family": "Lytrivi", "given": "Maria", "initials": "M"}, {"family": "Ghaddar", "given": "Kassem", "initials": "K"}, {"family": "Lopes", "given": "Miguel", "initials": "M"}, {"family": "Rosengren", "given": "Victoria", "initials": "V"}, {"family": "Piron", "given": "Anthony", "initials": "A"}, {"family": "Yi", "given": "Xiaoyan", "initials": "X"}, {"family": "Johansson", "given": "Henrik", "initials": "H"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Igoillo-Esteve", "given": "Mariana", "initials": "M"}, {"family": "Cunha", "given": "Daniel A", "initials": "DA"}, {"family": "Marselli", "given": "Lorella", "initials": "L"}, {"family": "Marchetti", "given": "Piero", "initials": "P"}, {"family": "Orts\u00e4ter", "given": "Henrik", "initials": "H"}, {"family": "Eizirik", "given": "Decio L", "initials": "DL"}, {"family": "Cnop", "given": "Miriam", "initials": "M", "orcid": "0000-0002-5112-1692", "researcher": {"href": "https://publications.scilifelab.se/researcher/b0d855a049344a42bbb571e7c8e688b0.json"}}], "type": "journal article", "published": "2020-08-26", "journal": {"title": "BMC Genomics", "issn": "1471-2164", "volume": "21", "issue": "1", "pages": "590", "issn-l": "1471-2164"}, "abstract": "Prolonged exposure to elevated free fatty acids induces \u03b2-cell failure (lipotoxicity) and contributes to the pathogenesis of type 2 diabetes. In vitro exposure of \u03b2-cells to the saturated free fatty acid palmitate is a valuable model of lipotoxicity, reproducing features of \u03b2-cell failure observed in type 2 diabetes. In order to map the \u03b2-cell response to lipotoxicity, we combined RNA-sequencing of palmitate-treated human islets with iTRAQ proteomics of insulin-secreting INS-1E cells following a time course exposure to palmitate.\n\nCrossing transcriptome and proteome of palmitate-treated \u03b2-cells revealed 85 upregulated and 122 downregulated genes at both transcript and protein level. Pathway analysis identified lipid metabolism, oxidative stress, amino-acid metabolism and cell cycle pathways among the most enriched palmitate-modified pathways. Palmitate induced gene expression changes compatible with increased free fatty acid mitochondrial import and \u03b2-oxidation, decreased lipogenesis and modified cholesterol transport. Palmitate modified genes regulating endoplasmic reticulum (ER) function, ER-to-Golgi transport and ER stress pathways. Furthermore, palmitate modulated cAMP/protein kinase A (PKA) signaling, inhibiting expression of PKA anchoring proteins and downregulating the GLP-1 receptor. SLC7 family amino-acid transporters were upregulated in response to palmitate but this induction did not contribute to \u03b2-cell demise. To unravel critical mediators of lipotoxicity upstream of the palmitate-modified genes, we identified overrepresented transcription factor binding sites and performed network inference analysis. These identified LXR, PPAR\u03b1, FOXO1 and BACH1 as key transcription factors orchestrating the metabolic and oxidative stress responses to palmitate.\n\nThis is the first study to combine transcriptomic and sensitive time course proteomic profiling of palmitate-exposed \u03b2-cells. Our results provide comprehensive insight into gene and protein expression changes, corroborating and expanding beyond previous findings. The identification of critical drivers and pathways of the \u03b2-cell lipotoxic response points to novel therapeutic targets for type 2 diabetes.", "doi": "10.1186/s12864-020-07003-0", "pmid": "32847508", "labels": {"Global Proteomics and Proteogenomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1186/s12864-020-07003-0"}, {"db": "pmc", "key": "PMC7448506"}], "notes": [], "created": "2021-01-12T18:17:43.722Z", "modified": "2021-11-10T12:48:00.690Z"}, {"entity": "publication", "iuid": "d75ee3f3f06b4002a4b80630b7b4d38b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d75ee3f3f06b4002a4b80630b7b4d38b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d75ee3f3f06b4002a4b80630b7b4d38b"}}, "title": "Support systems to guide clinical decision-making in precision oncology: The Cancer Core Europe Molecular Tumor Board Portal.", "authors": [{"family": "Tamborero", "given": "David", "initials": "D"}, {"family": "Dienstmann", "given": "Rodrigo", "initials": "R"}, {"family": "Rachid", "given": "Maan Haj", "initials": "MH", "orcid": "0000-0002-6380-209X", "researcher": {"href": "https://publications.scilifelab.se/researcher/6930cd01f3aa4e3e9233d98108f27c7d.json"}}, {"family": "Boekel", "given": "Jorrit", "initials": "J"}, {"family": "Baird", "given": "Richard", "initials": "R", "orcid": "0000-0001-7071-6483", "researcher": {"href": "https://publications.scilifelab.se/researcher/11aa354bf2f74c4d8c31f3e0faf650db.json"}}, {"family": "Bra\u00f1a", "given": "Irene", "initials": "I"}, {"family": "De Petris", "given": "Luigi", "initials": "L"}, {"family": "Yachnin", "given": "Jeffrey", "initials": "J"}, {"family": "Massard", "given": "Christophe", "initials": "C"}, {"family": "Opdam", "given": "Frans L", "initials": "FL"}, {"family": "Schlenk", "given": "Richard", "initials": "R"}, {"family": "Vernieri", "given": "Claudio", "initials": "C"}, {"family": "Garralda", "given": "Elena", "initials": "E"}, {"family": "Masucci", "given": "Michele", "initials": "M"}, {"family": "Villalobos", "given": "Xenia", "initials": "X"}, {"family": "Chavarria", "given": "Elena", "initials": "E"}, {"family": "Cancer Core Europe consortium", "given": "", "initials": ""}, {"family": "Calvo", "given": "Fabien", "initials": "F"}, {"family": "Fr\u00f6hling", "given": "Stefan", "initials": "S", "orcid": "0000-0001-7907-4595", "researcher": {"href": "https://publications.scilifelab.se/researcher/cd46d3f4c2084ce7922ceb0220b09277.json"}}, {"family": "Eggermont", "given": "Alexander", "initials": "A"}, {"family": "Apolone", "given": "Giovanni", "initials": "G"}, {"family": "Voest", "given": "Emile E", "initials": "EE", "orcid": "0000-0001-8249-9586", "researcher": {"href": "https://publications.scilifelab.se/researcher/e5a8340e3b0445bea291f971e1c2c75e.json"}}, {"family": "Caldas", "given": "Carlos", "initials": "C", "orcid": "0000-0003-3547-1489", "researcher": {"href": "https://publications.scilifelab.se/researcher/0cc09ee06f6c4391ba062ac65e85cb55.json"}}, {"family": "Tabernero", "given": "Josep", "initials": "J", "orcid": "0000-0002-2495-8139", "researcher": {"href": "https://publications.scilifelab.se/researcher/c9be0e16fc3f415e92754a6135bfc164.json"}}, {"family": "Ernberg", "given": "Ingemar", "initials": "I"}, {"family": "Rodon", "given": "Jordi", "initials": "J"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}], "type": "letter", "published": "2020-07-00", "journal": {"title": "Nat. Med.", "issn": "1546-170X", "issn-l": "1078-8956", "volume": "26", "issue": "7", "pages": "992-994"}, "abstract": null, "doi": "10.1038/s41591-020-0969-2", "pmid": "32632195", "labels": {"Clinical Genomics Stockholm": "Collaborative", "Global Proteomics and Proteogenomics": "Technology development", "Bioinformatics Support for Computational Resources": "Service", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41591-020-0969-2"}], "notes": [], "created": "2020-08-17T08:24:21.940Z", "modified": "2024-01-16T13:48:42.261Z"}, {"entity": "publication", "iuid": "03e3bbe957834896bd6e68663e072109", "links": {"self": {"href": "https://publications.scilifelab.se/publication/03e3bbe957834896bd6e68663e072109.json"}, "display": {"href": "https://publications.scilifelab.se/publication/03e3bbe957834896bd6e68663e072109"}}, "title": "DEqMS: A Method for Accurate Variance Estimation in Differential Protein Expression Analysis.", "authors": [{"family": "Zhu", "given": "Yafeng", "initials": "Y"}, {"family": "Orre", "given": "Lukas M", "initials": "LM", "orcid": "0000-0002-0384-1003", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b4e49a93b0143db88059c4d1e9fdc59.json"}}, {"family": "Zhou Tran", "given": "Yan", "initials": "Y"}, {"family": "Mermelekas", "given": "Georgios", "initials": "G"}, {"family": "Johansson", "given": "Henrik J", "initials": "HJ"}, {"family": "Malyutina", "given": "Alina", "initials": "A"}, {"family": "Anders", "given": "Simon", "initials": "S", "orcid": "0000-0003-4868-1805", "researcher": {"href": "https://publications.scilifelab.se/researcher/c11e0cc8bbb846ac821dcd782024c0cc.json"}}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}], "type": "journal article", "published": "2020-06-00", "journal": {"title": "Mol. Cell Proteomics", "issn": "1535-9484", "volume": "19", "issue": "6", "pages": "1047-1057", "issn-l": "1535-9476"}, "abstract": "Quantitative proteomics by mass spectrometry is widely used in biomarker research and basic biology research for investigation of phenotype level cellular events. Despite the wide application, the methodology for statistical analysis of differentially expressed proteins has not been unified. Various methods such as t test, linear model and mixed effect models are used to define changes in proteomics experiments. However, none of these methods consider the specific structure of MS-data. Choices between methods, often originally developed for other types of data, are based on compromises between features such as statistical power, general applicability and user friendliness. Furthermore, whether to include proteins identified with one peptide in statistical analysis of differential protein expression varies between studies. Here we present DEqMS, a robust statistical method developed specifically for differential protein expression analysis in mass spectrometry data. In all data sets investigated there is a clear dependence of variance on the number of PSMs or peptides used for protein quantification. DEqMS takes this feature into account when assessing differential protein expression. This allows for a more accurate data-dependent estimation of protein variance and inclusion of single peptide identifications without increasing false discoveries. The method was tested in several data sets including E. coli proteome spike-in data, using both label-free and TMT-labeled quantification. Compared with previous statistical methods used in quantitative proteomics, DEqMS showed consistently better accuracy in detecting altered protein levels compared with other statistical methods in both label-free and labeled quantitative proteomics data. DEqMS is available as an R package in Bioconductor.", "doi": "10.1074/mcp.TIR119.001646", "pmid": "32205417", "labels": {"Global Proteomics and Proteogenomics": "Technology development"}, "xrefs": [{"db": "pii", "key": "S1535-9476(20)34997-5"}, {"db": "pmc", "key": "PMC7261819"}], "notes": [], "created": "2021-01-12T18:14:40.770Z", "modified": "2021-11-10T12:50:41.761Z"}, {"entity": "publication", "iuid": "cde1f74c4f7c4f958deb3b63f5280f49", "links": {"self": {"href": "https://publications.scilifelab.se/publication/cde1f74c4f7c4f958deb3b63f5280f49.json"}, "display": {"href": "https://publications.scilifelab.se/publication/cde1f74c4f7c4f958deb3b63f5280f49"}}, "title": "Cell Cycle Profiling Reveals Protein Oscillation, Phosphorylation, and Localization Dynamics.", "authors": [{"family": "Herr", "given": "Patrick", "initials": "P", "orcid": "0000-0003-2945-966X", "researcher": {"href": "https://publications.scilifelab.se/researcher/ab7a8452d9464b48a74737f6615df015.json"}}, {"family": "Bostr\u00f6m", "given": "Johan", "initials": "J", "orcid": "0000-0001-5252-4023", "researcher": {"href": "https://publications.scilifelab.se/researcher/2af59464d2c74c27af7a43fb5d1a670e.json"}}, {"family": "Rullman", "given": "Eric", "initials": "E"}, {"family": "Rudd", "given": "Sean G", "initials": "SG", "orcid": "0000-0002-4368-3855", "researcher": {"href": "https://publications.scilifelab.se/researcher/cf1e23d9748e4868a4b5e966e423b1a9.json"}}, {"family": "Vesterlund", "given": "Mattias", "initials": "M", "orcid": "0000-0001-9471-6592", "researcher": {"href": "https://publications.scilifelab.se/researcher/0942e438993b494db2a3db914852c808.json"}}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7256c271ea4adea404d4ff355f804e.json"}}, {"family": "Maddalo", "given": "Gianluca", "initials": "G"}, {"family": "Altun", "given": "Mikael", "initials": "M", "orcid": "0000-0002-6937-6124", "researcher": {"href": "https://publications.scilifelab.se/researcher/4317b773615e476694840e907b7b1a0c.json"}}], "type": "journal article", "published": "2020-04-00", "journal": {"title": "Mol. Cell Proteomics", "issn": "1535-9484", "volume": "19", "issue": "4", "pages": "608-623", "issn-l": "1535-9476"}, "abstract": "The cell cycle is a highly conserved process involving the coordinated separation of a single cell into two daughter cells. To relate transcriptional regulation across the cell cycle with oscillatory changes in protein abundance and activity, we carried out a proteome- and phospho-proteome-wide mass spectrometry profiling. We compared protein dynamics with gene transcription, revealing many transcriptionally regulated G2 mRNAs that only produce a protein shift after mitosis. Integration of CRISPR/Cas9 survivability studies further highlighted proteins essential for cell viability. Analyzing the dynamics of phosphorylation events and protein solubility dynamics over the cell cycle, we characterize predicted phospho-peptide motif distributions and predict cell cycle-dependent translocating proteins, as exemplified by the S-adenosylmethionine synthase MAT2A. Our study implicates this enzyme in translocating to the nucleus after the G1/S-checkpoint, which enables epigenetic histone methylation maintenance during DNA replication. Taken together, this data set provides a unique integrated resource with novel insights on cell cycle dynamics.", "doi": "10.1074/mcp.RA120.001938", "pmid": "32051232", "labels": {"Global Proteomics and Proteogenomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S1535-9476(20)35020-9"}, {"db": "pmc", "key": "PMC7124475"}], "notes": [], "created": "2021-01-12T18:12:04.346Z", "modified": "2021-11-10T12:52:39.295Z"}, {"entity": "publication", "iuid": "2f4e1e715e8a4083a08bb02c679a5334", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2f4e1e715e8a4083a08bb02c679a5334.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2f4e1e715e8a4083a08bb02c679a5334"}}, "title": "Ribonucleotide reductase inhibitors suppress SAMHD1 ara-CTPase activity enhancing cytarabine efficacy.", "authors": [{"family": "Rudd", "given": "Sean G", "initials": "SG", "orcid": "0000-0002-4368-3855", "researcher": {"href": "https://publications.scilifelab.se/researcher/cf1e23d9748e4868a4b5e966e423b1a9.json"}}, {"family": "Tsesmetzis", "given": "Nikolaos", "initials": "N"}, {"family": "Sanjiv", "given": "Kumar", "initials": "K"}, {"family": "Paulin", "given": "Cynthia Bj", "initials": "CB"}, {"family": "Sandhow", "given": "Lakshmi", "initials": "L"}, {"family": "Kutzner", "given": "Juliane", "initials": "J"}, {"family": "Hed Myrberg", "given": "Ida", "initials": "I", "orcid": "0000-0002-8297-2238", "researcher": {"href": "https://publications.scilifelab.se/researcher/276d5d941a3e423cb82b8242eb375cc3.json"}}, {"family": "Bunten", "given": "Sarah S", "initials": "SS"}, {"family": "Axelsson", "given": "Hanna", "initials": "H", "orcid": "0000-0003-2365-1749", "researcher": {"href": "https://publications.scilifelab.se/researcher/63b88c4d11c443f39121c6d93fcff1f0.json"}}, {"family": "Zhang", "given": "Si Min", "initials": "SM"}, {"family": "Rasti", "given": "Azita", "initials": "A"}, {"family": "M\u00e4kel\u00e4", "given": "Petri", "initials": "P"}, {"family": "Coggins", "given": "Si'Ana A", "initials": "SA"}, {"family": "Tao", "given": "Sijia", "initials": "S"}, {"family": "Suman", "given": "Sharda", "initials": "S"}, {"family": "Branca", "given": "Rui M", "initials": "RM"}, {"family": "Mermelekas", "given": "Georgios", "initials": "G"}, {"family": "Wiita", "given": "Elis\u00e9e", "initials": "E"}, {"family": "Lee", "given": "Sun", "initials": "S"}, {"family": "Walfridsson", "given": "Julian", "initials": "J"}, {"family": "Schinazi", "given": "Raymond F", "initials": "RF"}, {"family": "Kim", "given": "Baek", "initials": "B"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Rassidakis", "given": "Georgios Z", "initials": "GZ"}, {"family": "Pokrovskaja Tamm", "given": "Katja", "initials": "K"}, {"family": "Warpman-Berglund", "given": "Ulrika", "initials": "U"}, {"family": "Heyman", "given": "Mats", "initials": "M"}, {"family": "Grand\u00e9r", "given": "Dan", "initials": "D"}, {"family": "Lehmann", "given": "S\u00f6ren", "initials": "S"}, {"family": "Lundb\u00e4ck", "given": "Thomas", "initials": "T"}, {"family": "Qian", "given": "Hong", "initials": "H"}, {"family": "Henter", "given": "Jan-Inge", "initials": "JI", "orcid": "0000-0002-0629-2126", "researcher": {"href": "https://publications.scilifelab.se/researcher/c1a0d663491c4665a32a612e423dff1b.json"}}, {"family": "Schaller", "given": "Torsten", "initials": "T", "orcid": "0000-0001-9597-4112", "researcher": {"href": "https://publications.scilifelab.se/researcher/c74944db1b4f4fe4a09079f417f8eec6.json"}}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7256c271ea4adea404d4ff355f804e.json"}}, {"family": "Herold", "given": "Nikolas", "initials": "N", "orcid": "0000-0001-9468-4543", "researcher": {"href": "https://publications.scilifelab.se/researcher/8a2af6f17f76457680908c36693f2de5.json"}}], "type": "journal article", "published": "2020-03-06", "journal": {"title": "EMBO Mol Med", "issn": "1757-4684", "volume": "12", "issue": "3", "pages": "e10419", "issn-l": "1757-4676"}, "abstract": "The deoxycytidine analogue cytarabine (ara-C) remains the backbone treatment of acute myeloid leukaemia (AML) as well as other haematological and lymphoid malignancies, but must be combined with other chemotherapeutics to achieve cure. Yet, the underlying mechanism dictating synergistic efficacy of combination chemotherapy remains largely unknown. The dNTPase SAMHD1, which regulates dNTP homoeostasis antagonistically to ribonucleotide reductase (RNR), limits ara-C efficacy by hydrolysing the active triphosphate metabolite ara-CTP. Here, we report that clinically used inhibitors of RNR, such as gemcitabine and hydroxyurea, overcome the SAMHD1-mediated barrier to ara-C efficacy in primary blasts and mouse models of AML, displaying SAMHD1-dependent synergy with ara-C. We present evidence that this is mediated by dNTP pool imbalances leading to allosteric reduction of SAMHD1 ara-CTPase activity. Thus, SAMHD1 constitutes a novel biomarker for combination therapies of ara-C and RNR inhibitors with immediate consequences for clinical practice to improve treatment of AML.", "doi": "10.15252/emmm.201910419", "pmid": "31950591", "labels": {"Chemical Biology Consortium Sweden": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC7059017"}], "notes": [], "created": "2020-11-08T14:42:08.378Z", "modified": "2025-10-17T13:04:28.335Z"}, {"entity": "publication", "iuid": "801a1c8a83fa4b0183e5729b84f7a003", "links": {"self": {"href": "https://publications.scilifelab.se/publication/801a1c8a83fa4b0183e5729b84f7a003.json"}, "display": {"href": "https://publications.scilifelab.se/publication/801a1c8a83fa4b0183e5729b84f7a003"}}, "title": "PCSK6 Is a Key Protease in the Control of Smooth Muscle Cell Function in Vascular Remodeling.", "authors": [{"family": "Rykaczewska", "given": "Urszula", "initials": "U"}, {"family": "Suur", "given": "Bianca E", "initials": "BE"}, {"family": "R\u00f6hl", "given": "Samuel", "initials": "S"}, {"family": "Razuvaev", "given": "Anton", "initials": "A"}, {"family": "Lengquist", "given": "Mariette", "initials": "M"}, {"family": "Sabater-Lleal", "given": "Maria", "initials": "M"}, {"family": "van der Laan", "given": "Sander W", "initials": "SW"}, {"family": "Miller", "given": "Clint L", "initials": "CL"}, {"family": "Wirka", "given": "Robert C", "initials": "RC"}, {"family": "Kronqvist", "given": "Malin", "initials": "M"}, {"family": "Gonzalez Diez", "given": "Maria", "initials": "M"}, {"family": "Vesterlund", "given": "Mattias", "initials": "M"}, {"family": "Gillgren", "given": "Peter", "initials": "P"}, {"family": "Odeberg", "given": "Jacob", "initials": "J"}, {"family": "Lindeman", "given": "Jan H", "initials": "JH"}, {"family": "Veglia", "given": "Fabrizio", "initials": "F"}, {"family": "Humphries", "given": "Steve E", "initials": "SE"}, {"family": "de Faire", "given": "Ulf", "initials": "U"}, {"family": "Baldassarre", "given": "Damiano", "initials": "D"}, {"family": "Tremoli", "given": "Elena", "initials": "E"}, {"family": "IMPROVE study group", "given": "", "initials": ""}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Hansson", "given": "G\u00f6ran K", "initials": "GK"}, {"family": "Paulsson-Berne", "given": "Gabrielle", "initials": "G"}, {"family": "Pasterkamp", "given": "Gerard", "initials": "G"}, {"family": "Quertermous", "given": "Thomas", "initials": "T"}, {"family": "Hamsten", "given": "Anders", "initials": "A"}, {"family": "Eriksson", "given": "Per", "initials": "P"}, {"family": "Hedin", "given": "Ulf", "initials": "U"}, {"family": "Matic", "given": "Ljubica", "initials": "L"}], "type": "journal article", "published": "2020-02-28", "journal": {"volume": "126", "issn": "1524-4571", "issue": "5", "title": "Circ. Res.", "pages": "571-585", "issn-l": "0009-7330"}, "abstract": "PCSKs (Proprotein convertase subtilisins/kexins) are a protease family with unknown functions in vasculature. Previously, we demonstrated PCSK6 upregulation in human atherosclerotic plaques associated with smooth muscle cells (SMCs), inflammation, extracellular matrix remodeling, and mitogens.\n\nHere, we applied a systems biology approach to gain deeper insights into the PCSK6 role in normal and diseased vessel wall.\n\nGenetic analyses revealed association of intronic PCSK6 variant rs1531817 with maximum internal carotid intima-media thickness progression in high-cardiovascular risk subjects. This variant was linked with PCSK6 mRNA expression in healthy aortas and plaques but also with overall plaque SMA+ cell content and pericyte fraction. Increased PCSK6 expression was found in several independent human cohorts comparing atherosclerotic lesions versus healthy arteries, using transcriptomic and proteomic datasets. By immunohistochemistry, PCSK6 was localized to fibrous cap SMA+ cells and neovessels in plaques. In human, rat, and mouse intimal hyperplasia, PCSK6 was expressed by proliferating SMA+ cells and upregulated after 5 days in rat carotid balloon injury model, with positive correlation to PDGFB (platelet-derived growth factor subunit B) and MMP (matrix metalloprotease) 2/MMP14. Here, PCSK6 was shown to colocalize and cointeract with MMP2/MMP14 by in situ proximity ligation assay. Microarrays of carotid arteries from Pcsk6-/- versus control mice revealed suppression of contractile SMC markers, extracellular matrix remodeling enzymes, and cytokines/receptors. Pcsk6-/- mice showed reduced intimal hyperplasia response upon carotid ligation in vivo, accompanied by decreased MMP14 activation and impaired SMC outgrowth from aortic rings ex vivo. PCSK6 silencing in human SMCs in vitro leads to downregulation of contractile markers and increase in MMP2 expression. Conversely, PCSK6 overexpression increased PDGFBB (platelet-derived growth factor BB)-induced cell proliferation and particularly migration.\n\nPCSK6 is a novel protease that induces SMC migration in response to PDGFB, mechanistically via modulation of contractile markers and MMP14 activation. This study establishes PCSK6 as a key regulator of SMC function in vascular remodeling. Visual Overview: An online visual overview is available for this article.", "doi": "10.1161/CIRCRESAHA.119.316063", "pmid": "31893970", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Global Proteomics and Proteogenomics": "Collaborative"}, "xrefs": [], "notes": [], "created": "2020-01-14T10:04:55.756Z", "modified": "2021-11-10T12:53:44.074Z"}, {"entity": "publication", "iuid": "170fec648fb448e99fbe3bd024cd7e34", "links": {"self": {"href": "https://publications.scilifelab.se/publication/170fec648fb448e99fbe3bd024cd7e34.json"}, "display": {"href": "https://publications.scilifelab.se/publication/170fec648fb448e99fbe3bd024cd7e34"}}, "title": "A Mitochondrial LYR Protein Is Required for Complex I Assembly.", "authors": [{"family": "Ivanova", "given": "Aneta", "initials": "A", "orcid": "0000-0002-2465-7213", "researcher": {"href": "https://publications.scilifelab.se/researcher/3b4791ef8f5843949894df534ff8355e.json"}}, {"family": "Gill-Hille", "given": "Mabel", "initials": "M", "orcid": "0000-0001-7749-5839", "researcher": {"href": "https://publications.scilifelab.se/researcher/7eb758e47fb34b8a86f076d1574c31b1.json"}}, {"family": "Huang", "given": "Shaobai", "initials": "S", "orcid": "0000-0003-3667-611X", "researcher": {"href": "https://publications.scilifelab.se/researcher/eee12c8a03254793b1735eb4510fc90f.json"}}, {"family": "Branca", "given": "Rui M", "initials": "RM", "orcid": "0000-0003-3890-6476", "researcher": {"href": "https://publications.scilifelab.se/researcher/87d6256540174d3da581d4572f9d182a.json"}}, {"family": "Kmiec", "given": "Beata", "initials": "B", "orcid": "0000-0002-1383-0412", "researcher": {"href": "https://publications.scilifelab.se/researcher/7cacde5eab9a4ce8ada537324ed66d05.json"}}, {"family": "Teixeira", "given": "Pedro F", "initials": "PF", "orcid": "0000-0001-8638-7477", "researcher": {"href": "https://publications.scilifelab.se/researcher/9b43730fe20b424db84f091333be7244.json"}}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Whelan", "given": "James", "initials": "J", "orcid": "0000-0001-5754-025X", "researcher": {"href": "https://publications.scilifelab.se/researcher/15d6dae558a24c03b6298dc9bd5b991d.json"}}, {"family": "Murcha", "given": "Monika W", "initials": "MW", "orcid": "0000-0002-3689-6158", "researcher": {"href": "https://publications.scilifelab.se/researcher/49b1e7e1fca74be090072ad2185c9827.json"}}], "type": "journal article", "published": "2019-12-00", "journal": {"volume": "181", "issn": "1532-2548", "issue": "4", "pages": "1632-1650", "title": "Plant Physiol.", "issn-l": "0032-0889"}, "abstract": "Complex I biogenesis requires the expression of both nuclear and mitochondrial genes, the import of proteins, cofactor biosynthesis, and the assembly of at least 49 individual subunits. Assembly factors interact with subunits of Complex I but are not part of the final holocomplex. We show that in Arabidopsis (Arabidopsis thaliana), a mitochondrial matrix protein (EMB1793, At1g76060), which we term COMPLEX I ASSEMBLY FACTOR 1 (CIAF1), contains a LYR domain and is required for Complex I assembly. T-DNA insertion mutants of CIAF1 lack Complex I and the Supercomplex I+III. Biochemical characterization shows that the assembly of Complex I is stalled at 650 and 800 kD intermediates in mitochondria isolated from ciaf1 mutant lines.I. Yeast-two-hybrid interaction and complementation assays indicate that CIAF1 specifically interacts with the 23-kD TYKY-1 matrix domain subunit of Complex I and likely plays a role in Fe-S insertion into this subunit. These data show that CIAF1 plays an essential role in assembling the peripheral matrix arm Complex I subunits into the Complex I holoenzyme.", "doi": "10.1104/pp.19.00822", "pmid": "31601645", "labels": {"Global Proteomics and Proteogenomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "pp.19.00822"}, {"db": "pmc", "key": "PMC6878026"}], "notes": [], "created": "2020-01-07T12:28:27.281Z", "modified": "2021-07-08T11:16:55.122Z"}, {"entity": "publication", "iuid": "f01e0637f7c24d9cab1f19d92d522e55", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f01e0637f7c24d9cab1f19d92d522e55.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f01e0637f7c24d9cab1f19d92d522e55"}}, "title": "Voluntary exercise normalizes the proteomic landscape in muscle and brain and improves the phenotype of progeroid mice.", "authors": [{"family": "Ross", "given": "Jaime M", "initials": "JM", "orcid": "0000-0002-3879-4817", "researcher": {"href": "https://publications.scilifelab.se/researcher/36fdacf781ea45ae88dd8dd5f046a314.json"}}, {"family": "Coppotelli", "given": "Giuseppe", "initials": "G"}, {"family": "Branca", "given": "Rui M", "initials": "RM"}, {"family": "Kim", "given": "Kyung M", "initials": "KM"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Sinclair", "given": "David A", "initials": "DA"}, {"family": "Olson", "given": "Lars", "initials": "L"}], "type": "journal article", "published": "2019-12-00", "journal": {"volume": "18", "issn": "1474-9726", "issue": "6", "pages": "e13029", "title": "Aging Cell", "issn-l": "1474-9718"}, "abstract": "The accumulation of mitochondrial DNA (mtDNA) mutations is a suspected driver of aging and age-related diseases, but forestalling these changes has been a major challenge. One of the best-studied models is the prematurely aging mtDNA mutator mouse, which carries a homozygous knock-in of a proofreading deficient version of the catalytic subunit of mtDNA polymerase-\u03b3 (PolgA). We investigated how voluntary exercise affects the progression of aging phenotypes in this mouse, focusing on mitochondrial and protein homeostasis in both brain and peripheral tissues. Voluntary exercise significantly ameliorated several aspects of the premature aging phenotype, including decreased locomotor activity, alopecia, and kyphosis, but did not have major effects on the decreased lifespan of mtDNA mutator mice. Exercise also decreased the mtDNA mutation load. In-depth tissue proteomics revealed that exercise normalized the levels of about half the proteins, with the majority involved in mitochondrial function and nuclear-mitochondrial crosstalk. There was also a specific increase in the nuclear-encoded proteins needed for the tricarboxylic acid cycle and complex II, but not in mitochondrial-encoded oxidative phosphorylation proteins, as well as normalization of enzymes involved in coenzyme Q biosynthesis. Furthermore, we found tissue-specific alterations, with brain coping better as compared to muscle and with motor cortex being better protected than striatum, in response to mitochondrial dysfunction. We conclude that voluntary exercise counteracts aging in mtDNA mutator mice by counteracting protein dysregulation in muscle and brain, decreasing the mtDNA mutation burden in muscle, and delaying overt aging phenotypes.", "doi": "10.1111/acel.13029", "pmid": "31489782", "labels": {"Global Proteomics and Proteogenomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC6826127"}], "notes": [], "created": "2020-01-07T12:28:28.162Z", "modified": "2021-07-08T11:26:52.847Z"}, {"entity": "publication", "iuid": "cf7bf4bafff647f7ab3501fe1e844770", "links": {"self": {"href": "https://publications.scilifelab.se/publication/cf7bf4bafff647f7ab3501fe1e844770.json"}, "display": {"href": "https://publications.scilifelab.se/publication/cf7bf4bafff647f7ab3501fe1e844770"}}, "title": "TcellSubC: An Atlas of the Subcellular Proteome of Human T Cells.", "authors": [{"family": "Joshi", "given": "Rubin Narayan", "initials": "RN"}, {"family": "Stadler", "given": "Charlotte", "initials": "C", "orcid": "0000-0002-6781-1938", "researcher": {"href": "https://publications.scilifelab.se/researcher/2db3b27c7d7143cbacc8c1dd8ac90a31.json"}}, {"family": "Lehmann", "given": "Robert", "initials": "R"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Tegn\u00e9r", "given": "Jesper", "initials": "J"}, {"family": "Schmidt", "given": "Angelika", "initials": "A"}, {"family": "Vesterlund", "given": "Mattias", "initials": "M"}], "type": "journal article", "published": "2019-11-26", "journal": {"volume": "10", "issn": "1664-3224", "issue": null, "pages": "2708", "title": "Front Immunol", "issn-l": "1664-3224"}, "abstract": "We have curated an in-depth subcellular proteomic map of primary human CD4+ T cells, divided into cytosolic, nuclear and membrane fractions generated by an optimized fractionation and HiRIEF-LC-MS/MS workflow for limited amounts of primary cells. The subcellular proteome of T cells was mapped under steady state conditions, as well as upon 15 min and 1 h of T cell receptor (TCR) stimulation, respectively. We quantified the subcellular distribution of 6,572 proteins and identified a subset of 237 potentially translocating proteins, including both well-known examples and novel ones. Microscopic validation confirmed the localization of selected proteins with previously known and unknown localization, respectively. We further provide the data in an easy-to-use web platform to facilitate re-use, as the data can be relevant for basic research as well as for clinical exploitation of T cells as therapeutic targets.", "doi": "10.3389/fimmu.2019.02708", "pmid": "31849937", "labels": {"Bioinformatics Support, Infrastructure and Training": "Service", "Bioinformatics Support and Infrastructure": "Service", "Spatial Proteomics": "Collaborative", "Global Proteomics and Proteogenomics": "Technology development", "Bioinformatics (NBIS)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC6902019"}], "notes": [], "created": "2019-12-03T08:36:31.738Z", "modified": "2021-07-08T11:26:52.822Z"}, {"entity": "publication", "iuid": "ac91005e977e42ddb2695318f80c99d6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ac91005e977e42ddb2695318f80c99d6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ac91005e977e42ddb2695318f80c99d6"}}, "title": "MYCN-enhanced Oxidative and Glycolytic Metabolism Reveals Vulnerabilities for Targeting Neuroblastoma.", "authors": [{"family": "Oliynyk", "given": "Ganna", "initials": "G"}, {"family": "Ruiz-P\u00e9rez", "given": "Mar\u00eda Victoria", "initials": "MV"}, {"family": "Sainero-Alcolado", "given": "Lourdes", "initials": "L"}, {"family": "Dzieran", "given": "Johanna", "initials": "J"}, {"family": "Zirath", "given": "Hanna", "initials": "H"}, {"family": "Gallart-Ayala", "given": "H\u00e9ctor", "initials": "H"}, {"family": "Wheelock", "given": "Craig E", "initials": "CE"}, {"family": "Johansson", "given": "Henrik J", "initials": "HJ"}, {"family": "Nilsson", "given": "Roland", "initials": "R"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Arsenian-Henriksson", "given": "Marie", "initials": "M"}], "type": "journal article", "published": "2019-11-22", "journal": {"volume": "21", "issn": "2589-0042", "issue": null, "pages": "188-204", "title": "iScience", "issn-l": "2589-0042"}, "abstract": "In pediatric neuroblastoma, MYCN-amplification correlates to poor clinical outcome and new treatment options are needed for these patients. Identifying the metabolic adaptations crucial for tumor progression may be a promising strategy to discover novel therapeutic targets. Here, we have combined proteomics, gene expression profiling, functional analysis, and metabolic tracing to decipher the impact of MYCN on neuroblastoma cell metabolism. We found that high MYCN levels are correlated with altered expression of proteins involved in multiple metabolic processes, including enhanced glycolysis and increased oxidative phosphorylation. Unexpectedly, we discovered that MYCN-amplified cells showed de novo glutamine synthesis. Furthermore, inhibition of \u03b2-oxidation reduced the viability of MYCN-amplified cells in vitro and decreased tumor burden in vivo, while not affecting non-MYCN-amplified tumors. Our data provide information on metabolic processes in MYCN expressing tumors, which could be exploited for the development of novel targeted therapies.", "doi": "10.1016/j.isci.2019.10.020", "pmid": "31670074", "labels": {"Global Proteomics and Proteogenomics": "Collaborative", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "S2589-0042(19)30399-2"}, {"db": "pmc", "key": "PMC6889365"}], "notes": [], "created": "2020-01-07T12:28:26.367Z", "modified": "2024-01-16T13:48:43.469Z"}, {"entity": "publication", "iuid": "cfd3c5561c144ffc9b162d6817c51089", "links": {"self": {"href": "https://publications.scilifelab.se/publication/cfd3c5561c144ffc9b162d6817c51089.json"}, "display": {"href": "https://publications.scilifelab.se/publication/cfd3c5561c144ffc9b162d6817c51089"}}, "title": "Ouabain-regulated phosphoproteome reveals molecular mechanisms for Na+, K+\u2013ATPase control of cell adhesion, proliferation, and survival", "authors": [{"family": "Panizza", "given": "Elena", "initials": "E"}, {"family": "Zhang", "given": "Liang", "initials": "L"}, {"family": "Fontana", "given": "Jacopo Maria", "initials": "JM"}, {"family": "Hamada", "given": "Kozo", "initials": "K"}, {"family": "Svensson", "given": "Daniel", "initials": "D"}, {"family": "Akkuratov", "given": "Evgeny E", "initials": "EE"}, {"family": "Scott", "given": "Lena", "initials": "L"}, {"family": "Mikoshiba", "given": "Katsuhiko", "initials": "K"}, {"family": "Brismar", "given": "Hjalmar", "initials": "H", "orcid": "0000-0003-0578-4003", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ec23336e2ef4e298f340876f1136dce.json"}}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Aperia", "given": "Anita", "initials": "A"}], "type": "journal-article", "published": "2019-06-14", "journal": {"volume": null, "issn": "0892-6638", "issue": null, "pages": "fj.201900445R", "title": "The FASEB Journal", "issn-l": "0892-6638"}, "abstract": "The ion pump Na +, K+-ATPase (NKA) is a receptor for the cardiotonic steroid ouabain. Subsaturating concentration of ouabain triggers intracellular calcium oscillations, stimulates cell proliferation and adhesion, and protects from apoptosis. However, it is controversial whether ouabain-bound NKA is considered a signal transducer. To address this question, we performed a global analysis of protein phosphorylation in COS-7 cells, identifying 2580 regulated phosphorylation events on 1242 proteins upon 10- and 20-min treatment with ouabain. Regulated phosphorylated proteins include the inositol triphosphate receptor and stromal interaction molecule, which are essential for initiating calcium oscillations. Hierarchical clustering revealed that ouabain triggers a structured phosphorylation response that occurs in a well-defined, time-dependent manner and affects specific cellular processes, including cell proliferation and cell-cell junctions. We additionally identify regulation of the phosphorylation of several calcium and calmodulin-dependent protein kinases (CAMKs), including 2 sites of CAMK type II-\u03b3 (CAMK2G), a protein known to regulate apoptosis. To verify the significance of this result, CAMK2G was knocked down in primary kidney cells. CAMK2G knockdown impaired ouabain-dependent protection from apoptosis upon treatment with high glucose or serum deprivation. In conclusion, we establish NKA as the coordinator of a broad, tightly regulated phosphorylation response in cells and define CAMK2G as a downstream effector of NKA.-Panizza, E., Zhang, L., Fontana, J. M., Hamada, K., Svensson, D., Akkuratov, E. E., Scott, L., Mikoshiba, K., Brismar, H., Lehti\u00f6, J., Aperia, A. Ouabain-regulated phosphoproteome reveals molecular mechanisms for Na+, K+-ATPase control of cell adhesion, proliferation, and survival.", "doi": "10.1096/fj.201900445r", "pmid": "31199885", "labels": {"Global Proteomics and Proteogenomics": "Technology development", "Integrated Microscopy Technologies Stockholm": "Collaborative", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [], "notes": [], "created": "2019-06-28T14:20:29.201Z", "modified": "2024-01-16T13:48:44.251Z"}, {"entity": "publication", "iuid": "d81332752ac544d4a3f4e26a9be1bf56", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d81332752ac544d4a3f4e26a9be1bf56.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d81332752ac544d4a3f4e26a9be1bf56"}}, "title": "Systematic assessment of antibody selectivity in plasma based on a resource of enrichment profiles.", "authors": [{"family": "Fredolini", "given": "Claudia", "initials": "C", "orcid": "0000-0002-7674-2014", "researcher": {"href": "https://publications.scilifelab.se/researcher/40ac3a5823cb4f998cc8bdb96dcbf195.json"}}, {"family": "Bystr\u00f6m", "given": "Sanna", "initials": "S"}, {"family": "Sanchez-Rivera", "given": "Laura", "initials": "L"}, {"family": "Ioannou", "given": "Marina", "initials": "M"}, {"family": "Tamburro", "given": "Davide", "initials": "D"}, {"family": "Pont\u00e9n", "given": "Fredrik", "initials": "F"}, {"family": "Branca", "given": "Rui M", "initials": "RM"}, {"family": "Nilsson", "given": "Peter", "initials": "P", "orcid": "0000-0002-4657-8532", "researcher": {"href": "https://publications.scilifelab.se/researcher/799bcf1cf8cf451296f4535dd4ca9dc0.json"}}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Schwenk", "given": "Jochen M", "initials": "JM", "orcid": "0000-0001-8141-8449", "researcher": {"href": "https://publications.scilifelab.se/researcher/aba5822711b246b397fffacb7ae403b3.json"}}], "type": "journal article", "published": "2019-06-06", "journal": {"volume": "9", "issn": "2045-2322", "issue": "1", "pages": "8324", "title": "Sci Rep", "issn-l": "2045-2322"}, "abstract": "There is a strong need for procedures that enable context and application dependent validation of antibodies. Here, we applied a magnetic bead assisted workflow and immunoprecipitation mass spectrometry (IP-MS/MS) to assess antibody selectivity for the detection of proteins in human plasma. A resource was built on 414 IP experiments using 157 antibodies (targeting 120 unique proteins) in assays with heat-treated or untreated EDTA plasma. For each protein we determined their antibody related degrees of enrichment using z-scores and their frequencies of identification across all IP assays. Out of 1,313 unique endogenous proteins, 426 proteins (33%) were detected in >20% of IPs, and these background components were mainly comprised of proteins from the complement system. For 45% (70/157) of the tested antibodies, the expected target proteins were enriched (z-score \u2265 3). Among these 70 antibodies, 59 (84%) co-enriched other proteins beside the intended target and mainly due to sequence homology or protein abundance. We also detected protein interactions in plasma, and for IGFBP2 confirmed these using several antibodies and sandwich immunoassays. The protein enrichment data with plasma provide a very useful and yet lacking resource for the assessment of antibody selectivity. Our insights will contribute to a more informed use of affinity reagents for plasma proteomics assays.", "doi": "10.1038/s41598-019-43552-5", "pmid": "31171813", "labels": {"Autoimmunity and Serology Profiling": "Technology development", "Affinity Proteomics Stockholm": "Technology development", "Global Proteomics and Proteogenomics": "Technology development", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-019-43552-5"}, {"db": "pmc", "key": "PMC6554399"}], "notes": [], "created": "2019-11-06T15:11:37.992Z", "modified": "2024-01-16T13:48:44.259Z"}, {"entity": "publication", "iuid": "aa033e622fbc43ffb6090c29ba97d1a8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/aa033e622fbc43ffb6090c29ba97d1a8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/aa033e622fbc43ffb6090c29ba97d1a8"}}, "title": "The viral protein corona directs viral pathogenesis and amyloid aggregation.", "authors": [{"family": "Ezzat", "given": "Kariem", "initials": "K", "orcid": "0000-0003-4186-0675", "researcher": {"href": "https://publications.scilifelab.se/researcher/6f2f1d3d8a5d467c8fc3b95388e4c606.json"}}, {"family": "Pernemalm", "given": "Maria", "initials": "M", "orcid": "0000-0003-4624-031X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f15f303cb2044cfa81719700137e3603.json"}}, {"family": "P\u00e5lsson", "given": "Sandra", "initials": "S"}, {"family": "Roberts", "given": "Thomas C", "initials": "TC"}, {"family": "J\u00e4rver", "given": "Peter", "initials": "P"}, {"family": "Dondalska", "given": "Aleksandra", "initials": "A"}, {"family": "Bestas", "given": "Burcu", "initials": "B"}, {"family": "Sobkowiak", "given": "Michal J", "initials": "MJ"}, {"family": "Lev\u00e4nen", "given": "Bettina", "initials": "B"}, {"family": "Sk\u00f6ld", "given": "Magnus", "initials": "M"}, {"family": "Thompson", "given": "Elizabeth A", "initials": "EA"}, {"family": "Saher", "given": "Osama", "initials": "O"}, {"family": "Kari", "given": "Otto K", "initials": "OK"}, {"family": "Lajunen", "given": "Tatu", "initials": "T", "orcid": "0000-0001-6234-9193", "researcher": {"href": "https://publications.scilifelab.se/researcher/55d9cb27b0734ca496514762ed1627f0.json"}}, {"family": "Sverremark Ekstr\u00f6m", "given": "Eva", "initials": "E", "orcid": "0000-0001-6271-8681", "researcher": {"href": "https://publications.scilifelab.se/researcher/d7519ea4bf1f43dcab124c3d62b489db.json"}}, {"family": "Nilsson", "given": "Caroline", "initials": "C"}, {"family": "Ishchenko", "given": "Yevheniia", "initials": "Y"}, {"family": "Malm", "given": "Tarja", "initials": "T"}, {"family": "Wood", "given": "Matthew J A", "initials": "MJA"}, {"family": "Power", "given": "Ultan F", "initials": "UF", "orcid": "0000-0003-3246-3774", "researcher": {"href": "https://publications.scilifelab.se/researcher/e0d135555da74520a0d4b7733cd6ddd7.json"}}, {"family": "Masich", "given": "Sergej", "initials": "S"}, {"family": "Lind\u00e9n", "given": "Anders", "initials": "A"}, {"family": "Sandberg", "given": "Johan K", "initials": "JK", "orcid": "0000-0002-6275-0750", "researcher": {"href": "https://publications.scilifelab.se/researcher/7468c415a46645a3a4c3d28badcff954.json"}}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Spetz", "given": "Anna-Lena", "initials": "AL", "orcid": "0000-0003-3964-9512", "researcher": {"href": "https://publications.scilifelab.se/researcher/70270e32d48d486799cc9dd61e36a4f1.json"}}, {"family": "El Andaloussi", "given": "Samir", "initials": "S"}], "type": "journal article", "published": "2019-05-27", "journal": {"volume": "10", "issn": "2041-1723", "issue": "1", "pages": "2331", "title": "Nat Commun", "issn-l": "2041-1723"}, "abstract": "Artificial nanoparticles accumulate a protein corona layer in biological fluids, which significantly influences their bioactivity. As nanosized obligate intracellular parasites, viruses share many biophysical properties with artificial nanoparticles in extracellular environments and here we show that respiratory syncytial virus (RSV) and herpes simplex virus type 1 (HSV-1) accumulate a rich and distinctive protein corona in different biological fluids. Moreover, we show that corona pre-coating differentially affects viral infectivity and immune cell activation. In addition, we demonstrate that viruses bind amyloidogenic peptides in their corona and catalyze amyloid formation via surface-assisted heterogeneous nucleation. Importantly, we show that HSV-1 catalyzes the aggregation of the amyloid \u03b2-peptide (A\u03b242), a major constituent of amyloid plaques in Alzheimer's disease, in vitro and in animal models. Our results highlight the viral protein corona as an acquired structural layer that is critical for viral-host interactions and illustrate a mechanistic convergence between viral and amyloid pathologies.", "doi": "10.1038/s41467-019-10192-2", "pmid": "31133680", "labels": {"Global Proteomics and Proteogenomics": "Technology development", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-019-10192-2"}, {"db": "pmc", "key": "PMC6536551"}], "notes": [], "created": "2020-01-07T12:31:23.818Z", "modified": "2024-01-16T13:48:44.332Z"}, {"entity": "publication", "iuid": "9e94dfa9b92d448eabccf47bb68156e2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9e94dfa9b92d448eabccf47bb68156e2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9e94dfa9b92d448eabccf47bb68156e2"}}, "title": "Ultrasensitive Immunoprofiling of Plasma Extracellular Vesicles Identifies Syndecan-1 as a Potential Tool for Minimally Invasive Diagnosis of Glioma.", "authors": [{"family": "Indira Chandran", "given": "Vineesh", "initials": "V"}, {"family": "Welinder", "given": "Charlotte", "initials": "C", "orcid": "0000-0001-9626-0576", "researcher": {"href": "https://publications.scilifelab.se/researcher/924dc427398e4ba7b31eb5b4b47a89ca.json"}}, {"family": "M\u00e5nsson", "given": "Ann-Sofie", "initials": "AS"}, {"family": "Offer", "given": "Svenja", "initials": "S"}, {"family": "Freyhult", "given": "Eva", "initials": "E", "orcid": "0000-0003-0226-1047", "researcher": {"href": "https://publications.scilifelab.se/researcher/be110f11a53d4dcfa3bfd1657167895e.json"}}, {"family": "Pernemalm", "given": "Maria", "initials": "M", "orcid": "0000-0003-4624-031X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f15f303cb2044cfa81719700137e3603.json"}}, {"family": "Lund", "given": "Sigrid M", "initials": "SM"}, {"family": "Pedersen", "given": "Shona", "initials": "S", "orcid": "0000-0001-6636-0293", "researcher": {"href": "https://publications.scilifelab.se/researcher/0c9565eb33bc4f15bdefeb1e796a728f.json"}}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Marko-Varga", "given": "Gyorgy", "initials": "G"}, {"family": "Johansson", "given": "Maria C", "initials": "MC"}, {"family": "Englund", "given": "Elisabet", "initials": "E", "orcid": "0000-0002-2708-2443", "researcher": {"href": "https://publications.scilifelab.se/researcher/8c98fa2b2e7e4e318cd00eb1e8e3ac7a.json"}}, {"family": "Sundgren", "given": "Pia C", "initials": "PC", "orcid": "0000-0001-9237-1236", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7c755205abb4ecfabb3d5f021b7a1f6.json"}}, {"family": "Belting", "given": "Mattias", "initials": "M"}], "type": "journal article", "published": "2019-05-15", "journal": {"volume": "25", "issn": "1557-3265", "issue": "10", "title": "Clin. Cancer Res.", "pages": "3115-3127", "issn-l": "1078-0432"}, "abstract": "Liquid biopsy has great potential to improve the management of brain tumor patients at high risk of surgery-associated complications. Here, the aim was to explore plasma extracellular vesicle (plEV) immunoprofiling as a tool for noninvasive diagnosis of glioma.\n\nPlEV isolation and analysis were optimized using advanced mass spectrometry, nanoparticle tracking analysis, and electron microscopy. We then established a new procedure that combines size exclusion chromatography isolation and proximity extension assay-based ultrasensitive immunoprofiling of plEV proteins that was applied on a well-defined glioma study cohort (n = 82).\n\nAmong potential candidates, we for the first time identify syndecan-1 (SDC1) as a plEV constituent that can discriminate between high-grade glioblastoma multiforme (GBM, WHO grade IV) and low-grade glioma [LGG, WHO grade II; area under the ROC curve (AUC): 0.81; sensitivity: 71%; specificity: 91%]. These findings were independently validated by ELISA. Tumor SDC1 mRNA expression similarly discriminated between GBM and LGG in an independent glioma patient population from The Cancer Genome Atlas cohort (AUC: 0.91; sensitivity: 79%; specificity: 91%). In experimental studies with GBM cells, we show that SDC1 is efficiently sorted to secreted EVs. Importantly, we found strong support of plEVSDC1 originating from GBM tumors, as plEVSDC1 correlated with SDC1 protein expression in matched patient tumors, and plEVSDC1 was decreased postoperatively depending on the extent of surgery.\n\nOur studies support the concept of circulating plEVs as a tool for noninvasive diagnosis and monitoring of gliomas and should move this field closer to the goal of improving the management of cancer patients.", "doi": "10.1158/1078-0432.CCR-18-2946", "pmid": "30679164", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Support and Infrastructure": "Collaborative", "Global Proteomics and Proteogenomics": "Technology development", "Structural Proteomics": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "1078-0432.CCR-18-2946"}], "notes": [], "created": "2019-02-01T09:02:21.138Z", "modified": "2021-07-08T11:26:52.783Z"}, {"entity": "publication", "iuid": "e7f90faca0e64cfe9379be8900367d06", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e7f90faca0e64cfe9379be8900367d06.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e7f90faca0e64cfe9379be8900367d06"}}, "title": "Breast cancer quantitative proteome and proteogenomic landscape.", "authors": [{"family": "Johansson", "given": "Henrik J", "initials": "HJ", "orcid": "0000-0003-4729-4205", "researcher": {"href": "https://publications.scilifelab.se/researcher/18aebf211fa640f48a7c8d860c168e5a.json"}}, {"family": "Socciarelli", "given": "Fabio", "initials": "F"}, {"family": "Vacanti", "given": "Nathaniel M", "initials": "NM"}, {"family": "Haugen", "given": "Mads H", "initials": "MH"}, {"family": "Zhu", "given": "Yafeng", "initials": "Y"}, {"family": "Siavelis", "given": "Ioannis", "initials": "I"}, {"family": "Fernandez-Woodbridge", "given": "Alejandro", "initials": "A"}, {"family": "Aure", "given": "Miriam R", "initials": "MR"}, {"family": "Sennblad", "given": "Bengt", "initials": "B"}, {"family": "Vesterlund", "given": "Mattias", "initials": "M", "orcid": "0000-0001-9471-6592", "researcher": {"href": "https://publications.scilifelab.se/researcher/0942e438993b494db2a3db914852c808.json"}}, {"family": "Branca", "given": "Rui M", "initials": "RM", "orcid": "0000-0003-3890-6476", "researcher": {"href": "https://publications.scilifelab.se/researcher/87d6256540174d3da581d4572f9d182a.json"}}, {"family": "Orre", "given": "Lukas M", "initials": "LM"}, {"family": "Huss", "given": "Mikael", "initials": "M"}, {"family": "Fredlund", "given": "Erik", "initials": "E"}, {"family": "Beraki", "given": "Elsa", "initials": "E"}, {"family": "Garred", "given": "\u00d8ystein", "initials": "\u00d8"}, {"family": "Boekel", "given": "Jorrit", "initials": "J"}, {"family": "Sauer", "given": "Torill", "initials": "T"}, {"family": "Zhao", "given": "Wei", "initials": "W"}, {"family": "Nord", "given": "Silje", "initials": "S"}, {"family": "H\u00f6glander", "given": "Elen K", "initials": "EK"}, {"family": "Jans", "given": "Daniel C", "initials": "DC"}, {"family": "Brismar", "given": "Hjalmar", "initials": "H", "orcid": "0000-0003-0578-4003", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ec23336e2ef4e298f340876f1136dce.json"}}, {"family": "Haukaas", "given": "Tonje H", "initials": "TH"}, {"family": "Bathen", "given": "Tone F", "initials": "TF"}, {"family": "Schlichting", "given": "Ellen", "initials": "E"}, {"family": "Naume", "given": "Bj\u00f8rn", "initials": "B"}, {"family": "Consortia Oslo Breast Cancer Research Consortium (OSBREAC)", "given": "", "initials": ""}, {"family": "Luders", "given": "Torben", "initials": "T"}, {"family": "Borgen", "given": "Elin", "initials": "E"}, {"family": "Kristensen", "given": "Vessela N", "initials": "VN"}, {"family": "Russnes", "given": "Hege G", "initials": "HG"}, {"family": "Lingj\u00e6rde", "given": "Ole Christian", "initials": "OC", "orcid": "0000-0003-3565-4912", "researcher": {"href": "https://publications.scilifelab.se/researcher/759346ec4321470f96ca42af68ed760c.json"}}, {"family": "Mills", "given": "Gordon B", "initials": "GB"}, {"family": "Sahlberg", "given": "Kristine K", "initials": "KK"}, {"family": "B\u00f8rresen-Dale", "given": "Anne-Lise", "initials": "AL"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}], "type": "journal article", "published": "2019-04-08", "journal": {"volume": "10", "issn": "2041-1723", "issue": "1", "pages": "1600", "title": "Nat Commun", "issn-l": "2041-1723"}, "abstract": "In the preceding decades, molecular characterization has revolutionized breast cancer (BC) research and therapeutic approaches. Presented herein, an unbiased analysis of breast tumor proteomes, inclusive of 9995 proteins quantified across all tumors, for the first time recapitulates BC subtypes. Additionally, poor-prognosis basal-like and luminal B tumors are further subdivided by immune component infiltration, suggesting the current classification is incomplete. Proteome-based networks distinguish functional protein modules for breast tumor groups, with co-expression of EGFR and MET marking ductal carcinoma in situ regions of normal-like tumors and lending to a more accurate classification of this poorly defined subtype. Genes included within prognostic mRNA panels have significantly higher than average mRNA-protein correlations, and gene copy number alterations are dampened at the protein-level; underscoring the value of proteome quantification for prognostication and phenotypic classification. Furthermore, protein products mapping to non-coding genomic regions are identified; highlighting a potential new class of tumor-specific immunotherapeutic targets.", "doi": "10.1038/s41467-019-09018-y", "pmid": "30962452", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Long-term Support WABI": "Collaborative", "Global Proteomics and Proteogenomics": "Technology development", "Integrated Microscopy Technologies Stockholm": "Service", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-019-09018-y"}, {"db": "pmc", "key": "PMC6453966"}], "notes": [], "created": "2019-04-12T07:18:25.320Z", "modified": "2024-01-16T13:48:44.506Z"}, {"entity": "publication", "iuid": "18fd999856294d44be3211726b2f3dc5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/18fd999856294d44be3211726b2f3dc5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/18fd999856294d44be3211726b2f3dc5"}}, "title": "Proteogenomics and Hi-C reveal transcriptional dysregulation in high hyperdiploid childhood acute lymphoblastic leukemia.", "authors": [{"family": "Yang", "given": "Minjun", "initials": "M", "orcid": "0000-0002-3324-1498", "researcher": {"href": "https://publications.scilifelab.se/researcher/62822d0b9c6c4a01a53829b9b05443ba.json"}}, {"family": "Vesterlund", "given": "Mattias", "initials": "M", "orcid": "0000-0001-9471-6592", "researcher": {"href": "https://publications.scilifelab.se/researcher/0942e438993b494db2a3db914852c808.json"}}, {"family": "Siavelis", "given": "Ioannis", "initials": "I"}, {"family": "Moura-Castro", "given": "Larissa H", "initials": "LH"}, {"family": "Castor", "given": "Anders", "initials": "A"}, {"family": "Fioretos", "given": "Thoas", "initials": "T", "orcid": "0000-0002-3235-6154", "researcher": {"href": "https://publications.scilifelab.se/researcher/35a5c1b6023345c6b1317c590bf80680.json"}}, {"family": "Jafari", "given": "Rozbeh", "initials": "R", "orcid": "0000-0002-3396-4709", "researcher": {"href": "https://publications.scilifelab.se/researcher/481b2a2329634f9086cf52fb808edea5.json"}}, {"family": "Lilljebj\u00f6rn", "given": "Henrik", "initials": "H", "orcid": "0000-0001-8703-1173", "researcher": {"href": "https://publications.scilifelab.se/researcher/b3a75300e8c346858ce8dd8f64ecae85.json"}}, {"family": "Odom", "given": "Duncan T", "initials": "DT", "orcid": "0000-0001-6201-5599", "researcher": {"href": "https://publications.scilifelab.se/researcher/a82aabbc9a42473a985e49eb1b184b6a.json"}}, {"family": "Olsson", "given": "Linda", "initials": "L"}, {"family": "Ravi", "given": "Naveen", "initials": "N"}, {"family": "Woodward", "given": "Eleanor L", "initials": "EL"}, {"family": "Harewood", "given": "Louise", "initials": "L"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Paulsson", "given": "Kajsa", "initials": "K", "orcid": "0000-0001-7950-222X", "researcher": {"href": "https://publications.scilifelab.se/researcher/2033b23811f1432c90ad860dd993e7a8.json"}}], "type": "journal article", "published": "2019-04-03", "journal": {"volume": "10", "issn": "2041-1723", "issue": "1", "pages": "1519", "title": "Nat Commun", "issn-l": "2041-1723"}, "abstract": "Hyperdiploidy, i.e. gain of whole chromosomes, is one of the most common genetic features of childhood acute lymphoblastic leukemia (ALL), but its pathogenetic impact is poorly understood. Here, we report a proteogenomic analysis on matched datasets from genomic profiling, RNA-sequencing, and mass spectrometry-based analysis of >8,000 genes and proteins as well as Hi-C of primary patient samples from hyperdiploid and ETV6/RUNX1-positive pediatric ALL. We show that CTCF and cohesin, which are master regulators of chromatin architecture, display low expression in hyperdiploid ALL. In line with this, a general genome-wide dysregulation of gene expression in relation to topologically associating domain (TAD) borders were seen in the hyperdiploid group. Furthermore, Hi-C of a limited number of hyperdiploid childhood ALL cases revealed that 2/4 cases displayed a clear loss of TAD boundary strength and 3/4 showed reduced insulation at TAD borders, with putative leukemogenic effects.", "doi": "10.1038/s41467-019-09469-3", "pmid": "30944321", "labels": {"Clinical Genomics Lund": "Service", "Global Proteomics and Proteogenomics": "Technology development", "Bioinformatics Support for Computational Resources": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-019-09469-3"}, {"db": "pmc", "key": "PMC6447538"}], "notes": [], "created": "2019-12-13T15:04:45.801Z", "modified": "2024-01-16T13:48:44.549Z"}, {"entity": "publication", "iuid": "ce017bfd92fb49769abbc2215c8978a0", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ce017bfd92fb49769abbc2215c8978a0.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ce017bfd92fb49769abbc2215c8978a0"}}, "title": "SubCellBarCode: Proteome-wide Mapping of Protein Localization and Relocalization.", "authors": [{"family": "Orre", "given": "Lukas Minus", "initials": "LM"}, {"family": "Vesterlund", "given": "Mattias", "initials": "M"}, {"family": "Pan", "given": "Yanbo", "initials": "Y"}, {"family": "Arslan", "given": "Taner", "initials": "T"}, {"family": "Zhu", "given": "Yafeng", "initials": "Y"}, {"family": "Fernandez Woodbridge", "given": "Alejandro", "initials": "A"}, {"family": "Frings", "given": "Oliver", "initials": "O"}, {"family": "Fredlund", "given": "Erik", "initials": "E"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}], "type": "journal article", "published": "2019-01-03", "journal": {"volume": "73", "issn": "1097-4164", "issue": "1", "pages": "166-182.e7", "title": "Mol. Cell", "issn-l": "1097-2765"}, "abstract": "Subcellular localization is a main determinant of protein function; however, a global view of cellular proteome organization remains relatively unexplored. We have developed a robust mass spectrometry-based analysis pipeline to generate a proteome-wide view of subcellular localization for proteins mapping to 12,418 individual genes across five cell lines. Based on more than 83,000 unique classifications and correlation profiling, we investigate the effect of alternative splicing and protein domains on localization, complex member co-localization, cell-type-specific localization, as well as protein relocalization after growth factor inhibition. Our analysis provides information about the cellular architecture and complexity of the spatial organization of the proteome; we show that the majority of proteins have a single main subcellular location, that alternative splicing rarely affects subcellular location, and that cell types are best distinguished by expression of proteins exposed to the surrounding environment. The resource is freely accessible via www.subcellbarcode.org.", "doi": "10.1016/j.molcel.2018.11.035", "pmid": "30609389", "labels": {"Global Proteomics and Proteogenomics": "Technology development", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "S1097-2765(18)31005-0"}], "notes": [], "created": "2019-01-07T11:26:59.608Z", "modified": "2024-01-16T13:48:44.861Z"}, {"entity": "publication", "iuid": "c513594b717d41568e7a836fb7437a2f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c513594b717d41568e7a836fb7437a2f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c513594b717d41568e7a836fb7437a2f"}}, "title": "Extracellular nanovesicles released from the commensal yeast Malassezia sympodialis are enriched in allergens and interact with cells in human skin", "authors": [{"family": "Johansson", "given": "Henrik J", "initials": "HJ"}, {"family": "Vallhov", "given": "Helen", "initials": "H"}, {"family": "Holm", "given": "Tina", "initials": "T"}, {"family": "Gehrmann", "given": "Ulf", "initials": "U"}, {"family": "Andersson", "given": "Anna", "initials": "A"}, {"family": "Johansson", "given": "Catharina", "initials": "C"}, {"family": "Blom", "given": "Hans", "initials": "H", "orcid": "0000-0002-5584-9170", "researcher": {"href": "https://publications.scilifelab.se/researcher/3ce356a74dc84e0ea6af85397f11d869.json"}}, {"family": "Carroni", "given": "Marta", "initials": "M", "orcid": "0000-0002-7697-6427", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7f1bc1767024368abcb11a83184994a.json"}}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Scheynius", "given": "Annika", "initials": "A"}], "type": "journal-article", "published": "2018-12-00", "journal": {"volume": "8", "issn": "2045-2322", "issue": "1", "pages": null, "title": "Sci Rep", "issn-l": "2045-2322"}, "abstract": "Malassezia sympodialis is a dominant commensal fungi in the human skin mycobiome but is also associated with common skin disorders including atopic eczema (AE). M. sympodialis releases extracellular vesicles, designated MalaEx, which are carriers of small RNAs and allergens, and they can induce inflammatory cytokine responses. Here we explored how MalaEx are involved in host-microbe interactions by comparing protein content of MalaEx with that of the parental yeast cells, and by investigating interactions of MalaEx with cells in the skin. Cryo-electron tomography revealed a heterogeneous population of MalaEx. iTRAQ based quantitative proteomics identified in total 2439 proteins in all replicates of which 110 were enriched in MalaEx compared to the yeast cells. Among the MalaEx enriched proteins were two of the M. sympodialis allergens, Mala s 1 and s 7. Functional experiments indicated an active binding and internalization of MalaEx into human keratinocytes and monocytes, and MalaEx were found in close proximity of the nuclei using super-resolution fluorescence 3D-SIM imaging. Our results provides new insights into host-microbe interactions, supporting that MalaEx may have a role in the sensitization and maintenance of inflammation in AE by containing enriched amounts of allergens and with their ability to interact with skin cells.", "doi": "10.1038/s41598-018-27451-9", "pmid": "29907748", "labels": {"Cryo-EM": "Service", "Global Proteomics and Proteogenomics": "Collaborative", "Integrated Microscopy Technologies Stockholm": "Collaborative", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "jPOSTrepo", "description": "https://repository.jpostdb.org/entry/JPST000288", "key": "JPST000288"}], "notes": [], "created": "2018-06-20T09:34:38.559Z", "modified": "2024-01-16T13:48:45.085Z"}, {"entity": "publication", "iuid": "6c018d7fe577404c9ce7c148a8d5ecd4", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6c018d7fe577404c9ce7c148a8d5ecd4.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6c018d7fe577404c9ce7c148a8d5ecd4"}}, "title": "Single-Stranded Nucleic Acids Regulate TLR3/4/7 Activation through Interference with Clathrin-Mediated Endocytosis.", "authors": [{"family": "J\u00e4rver", "given": "Peter", "initials": "P", "orcid": "0000-0001-9643-5874", "researcher": {"href": "https://publications.scilifelab.se/researcher/7645ffd2a3f7458b805892f41fd1e124.json"}}, {"family": "Dondalska", "given": "Aleksandra", "initials": "A"}, {"family": "Poux", "given": "Candice", "initials": "C"}, {"family": "Sandberg", "given": "AnnSofi", "initials": "A"}, {"family": "Bergenstr\u00e5hle", "given": "Joseph", "initials": "J"}, {"family": "Sk\u00f6ld", "given": "Annette E", "initials": "AE"}, {"family": "Dereuddre-Bosquet", "given": "Nathalie", "initials": "N"}, {"family": "Martinon", "given": "Fr\u00e9deric", "initials": "F"}, {"family": "P\u00e5lsson", "given": "Sandra", "initials": "S"}, {"family": "Zaghloul", "given": "Eman", "initials": "E"}, {"family": "Brodin", "given": "David", "initials": "D"}, {"family": "Sander", "given": "Birgitta", "initials": "B"}, {"family": "Lennox", "given": "Kim A", "initials": "KA"}, {"family": "Behlke", "given": "Mark A", "initials": "MA"}, {"family": "El-Andaloussi", "given": "Samir", "initials": "S"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Lundeberg", "given": "Joakim", "initials": "J", "orcid": "0000-0003-4313-1601", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a4e6ca0f29b4ead8569e2729481c3e0.json"}}, {"family": "LeGrand", "given": "Roger", "initials": "R"}, {"family": "Spetz", "given": "Anna-Lena", "initials": "AL", "orcid": "0000-0003-3964-9512", "researcher": {"href": "https://publications.scilifelab.se/researcher/70270e32d48d486799cc9dd61e36a4f1.json"}}], "type": "journal article", "published": "2018-10-26", "journal": {"volume": "8", "issn": "2045-2322", "issue": "1", "pages": "15841", "title": "Sci Rep", "issn-l": "2045-2322"}, "abstract": "Recognition of nucleic acids by endosomal Toll-like receptors (TLR) is essential to combat pathogens, but requires strict control to limit inflammatory responses. The mechanisms governing this tight regulation are unclear. We found that single-stranded oligonucleotides (ssON) inhibit endocytic pathways used by cargo destined for TLR3/4/7 signaling endosomes. Both ssDNA and ssRNA conferred the endocytic inhibition, it was concentration dependent, and required a certain ssON length. The ssON-mediated inhibition modulated signaling downstream of TLRs that localized within the affected endosomal pathway. We further show that injection of ssON dampens dsRNA-mediated inflammatory responses in the skin of non-human primates. These studies reveal a regulatory role for extracellular ssON in the endocytic uptake of TLR ligands and provide a mechanistic explanation of their immunomodulation. The identified ssON-mediated interference of endocytosis (SOMIE) is a regulatory process that temporarily dampens TLR3/4/7 signaling, thereby averting excessive immune responses.", "doi": "10.1038/s41598-018-33960-4", "pmid": "30367171", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Global Proteomics and Proteogenomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-018-33960-4"}, {"db": "pmc", "key": "PMC6203749"}], "notes": [], "created": "2019-01-04T14:04:14.911Z", "modified": "2021-07-08T11:26:36.978Z"}, {"entity": "publication", "iuid": "aec47ed69c344e34b27de60b2b9d64f2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/aec47ed69c344e34b27de60b2b9d64f2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/aec47ed69c344e34b27de60b2b9d64f2"}}, "title": "Metabolic reprogramming of acute lymphoblastic leukemia cells in response to glucocorticoid treatment.", "authors": [{"family": "Dyczynski", "given": "Matheus", "initials": "M", "orcid": "0000-0002-7650-3574", "researcher": {"href": "https://publications.scilifelab.se/researcher/d6747a657a814238b47f2278bb71a115.json"}}, {"family": "Vesterlund", "given": "Mattias", "initials": "M"}, {"family": "Bj\u00f6rklund", "given": "Ann-Charlotte", "initials": "AC"}, {"family": "Zachariadis", "given": "Vasilios", "initials": "V"}, {"family": "Janssen", "given": "Jerry", "initials": "J"}, {"family": "Gallart-Ayala", "given": "Hector", "initials": "H"}, {"family": "Daskalaki", "given": "Evangelia", "initials": "E"}, {"family": "Wheelock", "given": "Craig E", "initials": "CE"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Grand\u00e9r", "given": "Dan", "initials": "D"}, {"family": "Tamm", "given": "Katja Pokrovskaja", "initials": "KP", "orcid": "0000-0001-6359-1256", "researcher": {"href": "https://publications.scilifelab.se/researcher/09ec3ee706764024bd748c7a77443845.json"}}, {"family": "Nilsson", "given": "Roland", "initials": "R", "orcid": "0000-0002-6020-7498", "researcher": {"href": "https://publications.scilifelab.se/researcher/0667c6d082934d818445fe0187dbb23e.json"}}], "type": "journal article", "published": "2018-08-28", "journal": {"volume": "9", "issn": "2041-4889", "issue": "9", "pages": "846", "title": "Cell Death Dis", "issn-l": "2041-4889"}, "abstract": "Glucocorticoids (GCs) are metabolic hormones with immunosuppressive effects that have proven effective drugs against childhood acute lymphoblastic leukemia (ALL). Yet, the role of metabolic reprogramming in GC-induced ALL cell death is poorly understood. GCs efficiently block glucose uptake and metabolism in ALL cells, but this does not fully explain the observed induction of autophagy and cell death. Here, we have performed parallel time-course proteomics, metabolomics, and isotope-tracing studies to examine in detail the metabolic effects of GCs on ALL cells. We observed metabolic events associated with growth arrest, autophagy, and catabolism prior to onset of apoptosis: nucleotide de novo synthesis was reduced, while certain nucleobases accumulated; polyamine synthesis was inhibited; and phosphatidylcholine synthesis was induced. GCs suppressed not only glycolysis but also entry of both glucose and glutamine into the TCA cycle. In contrast, expression of glutamine-ammonia ligase (GLUL) and cellular glutamine content was robustly increased by GC treatment, suggesting induction of glutamine synthesis, similar to nutrient-starved muscle. Modulating medium glutamine and dimethyl-\u03b1-ketoglutarate (dm-\u03b1kg) to favor glutamine synthesis reduced autophagosome content of ALL cells, and dm-\u03b1kg also rescued cell viability. These data suggest that glutamine synthesis affects autophagy and possibly onset of cell death in response to GCs, which should be further explored to understand mechanism of action and possible sources of resistance.", "doi": "10.1038/s41419-018-0625-7", "pmid": "30154400", "labels": {"Global Proteomics and Proteogenomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41419-018-0625-7"}, {"db": "pmc", "key": "PMC6113325"}], "notes": [], "created": "2019-01-07T11:35:25.267Z", "modified": "2021-07-08T11:27:41.315Z"}, {"entity": "publication", "iuid": "a9fb75889ad84b92be0b8a787275d4d3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a9fb75889ad84b92be0b8a787275d4d3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a9fb75889ad84b92be0b8a787275d4d3"}}, "title": "Novel Multiomics Profiling of Human Carotid Atherosclerotic Plaques and Plasma Reveals Biliverdin Reductase B as a Marker of Intraplaque Hemorrhage.", "authors": [{"family": "Matic", "given": "Ljubica Perisic", "initials": "LP"}, {"family": "Jesus Iglesias", "given": "Maria", "initials": "M"}, {"family": "Vesterlund", "given": "Mattias", "initials": "M"}, {"family": "Lengquist", "given": "Mariette", "initials": "M"}, {"family": "Hong", "given": "Mun-Gwan", "initials": "MG"}, {"family": "Saieed", "given": "Shanga", "initials": "S"}, {"family": "Sanchez-Rivera", "given": "Laura", "initials": "L"}, {"family": "Berg", "given": "Martin", "initials": "M"}, {"family": "Razuvaev", "given": "Anton", "initials": "A"}, {"family": "Kronqvist", "given": "Malin", "initials": "M"}, {"family": "Lund", "given": "Kent", "initials": "K"}, {"family": "Caidahl", "given": "Kenneth", "initials": "K"}, {"family": "Gillgren", "given": "Peter", "initials": "P"}, {"family": "Pont\u00e9n", "given": "Fredrik", "initials": "F"}, {"family": "Uhl\u00e9n", "given": "Mathias", "initials": "M"}, {"family": "Schwenk", "given": "Jochen M", "initials": "JM", "orcid": "0000-0001-8141-8449", "researcher": {"href": "https://publications.scilifelab.se/researcher/aba5822711b246b397fffacb7ae403b3.json"}}, {"family": "Hansson", "given": "G\u00f6ran K", "initials": "GK"}, {"family": "Paulsson-Berne", "given": "Gabrielle", "initials": "G"}, {"family": "Fagman", "given": "Erika", "initials": "E"}, {"family": "Roy", "given": "Joy", "initials": "J"}, {"family": "Hultgren", "given": "Rebecka", "initials": "R"}, {"family": "Bergstr\u00f6m", "given": "G\u00f6ran", "initials": "G"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Odeberg", "given": "Jacob", "initials": "J"}, {"family": "Hedin", "given": "Ulf", "initials": "U"}], "type": "journal article", "published": "2018-08-00", "journal": {"volume": "3", "issn": "2452-302X", "issue": "4", "pages": "464-480", "title": "JACC Basic Transl Sci", "issn-l": "2452-302X"}, "abstract": "Clinical tools to identify individuals with unstable atherosclerotic lesions are required to improve prevention of myocardial infarction and ischemic stroke. Here, a systems-based analysis of atherosclerotic plaques and plasma from patients undergoing carotid endarterectomy for stroke prevention was used to identify molecular signatures with a causal relationship to disease. Local plasma collected in the lesion proximity following clamping prior to arteriotomy was profiled together with matched peripheral plasma. This translational workflow identified biliverdin reductase B as a novel marker of intraplaque hemorrhage and unstable carotid atherosclerosis, which should be investigated as a potential predictive biomarker for cardiovascular events in larger cohorts.", "doi": "10.1016/j.jacbts.2018.04.001", "pmid": "30175270", "labels": {"Affinity Proteomics Stockholm": "Collaborative", "Global Proteomics and Proteogenomics": "Collaborative", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "S2452-302X(18)30096-2"}, {"db": "pmc", "key": "PMC6115646"}], "notes": [], "created": "2018-10-31T09:20:29.498Z", "modified": "2024-01-16T13:48:45.861Z"}, {"entity": "publication", "iuid": "c5ac8923292c4f80b7f141382febd809", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c5ac8923292c4f80b7f141382febd809.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c5ac8923292c4f80b7f141382febd809"}}, "title": "Heterogeneity and interplay of the extracellular vesicle small RNA transcriptome and proteome.", "authors": [{"family": "Sork", "given": "Helena", "initials": "H", "orcid": "0000-0002-5390-4420", "researcher": {"href": "https://publications.scilifelab.se/researcher/f5d08dad4f2d4ee0a3e3a8f060383da5.json"}}, {"family": "Corso", "given": "Giulia", "initials": "G"}, {"family": "Krjutskov", "given": "Kaarel", "initials": "K"}, {"family": "Johansson", "given": "Henrik J", "initials": "HJ", "orcid": "0000-0003-4729-4205", "researcher": {"href": "https://publications.scilifelab.se/researcher/18aebf211fa640f48a7c8d860c168e5a.json"}}, {"family": "Nordin", "given": "Joel Z", "initials": "JZ"}, {"family": "Wiklander", "given": "Oscar P B", "initials": "OPB"}, {"family": "Lee", "given": "Yi Xin Fiona", "initials": "YXF", "orcid": "0000-0002-9092-1932", "researcher": {"href": "https://publications.scilifelab.se/researcher/619d8471b5704b45bc8a35ee560b47f7.json"}}, {"family": "Westholm", "given": "Jakub Orzechowski", "initials": "JO", "orcid": "0000-0002-6849-6220", "researcher": {"href": "https://publications.scilifelab.se/researcher/161d8b5fb6734b33ad5f5590edbc0cff.json"}}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Wood", "given": "Matthew J A", "initials": "MJA"}, {"family": "M\u00e4ger", "given": "Imre", "initials": "I"}, {"family": "El Andaloussi", "given": "Samir", "initials": "S"}], "type": "journal article", "published": "2018-07-17", "journal": {"volume": "8", "issn": "2045-2322", "issue": "1", "pages": "10813", "title": "Sci Rep", "issn-l": "2045-2322"}, "abstract": "Extracellular vesicles (EVs) mediate cell-to-cell communication by delivering or displaying macromolecules to their recipient cells. While certain broad-spectrum EV effects reflect their protein cargo composition, others have been attributed to individual EV-loaded molecules such as specific miRNAs. In this work, we have investigated the contents of vesicular cargo using small RNA sequencing of cells and EVs from HEK293T, RD4, C2C12, Neuro2a and C17.2. The majority of RNA content in EVs (49-96%) corresponded to rRNA-, coding- and tRNA fragments, corroborating with our proteomic analysis of HEK293T and C2C12 EVs which showed an enrichment of ribosome and translation-related proteins. On the other hand, the overall proportion of vesicular small RNA was relatively low and variable (2-39%) and mostly comprised of miRNAs and sequences mapping to piRNA loci. Importantly, this is one of the few studies, which systematically links vesicular RNA and protein cargo of vesicles. Our data is particularly useful for future work in unravelling the biological mechanisms underlying vesicular RNA and protein sorting and serves as an important guide in developing EVs as carriers for RNA therapeutics.", "doi": "10.1038/s41598-018-28485-9", "pmid": "30018314", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Long-term Support WABI": "Collaborative", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Global Proteomics and Proteogenomics": "Collaborative", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-018-28485-9"}, {"db": "pmc", "key": "PMC6050237"}], "notes": [], "created": "2018-08-07T08:38:11.195Z", "modified": "2024-01-16T13:48:45.984Z"}, {"entity": "publication", "iuid": "e66120f3f3b04764beb8e0005b69df33", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e66120f3f3b04764beb8e0005b69df33.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e66120f3f3b04764beb8e0005b69df33"}}, "title": "Molecular profiles of oxyphilic and chief cell parathyroid adenoma.", "authors": [{"family": "Lu", "given": "Ming", "initials": "M"}, {"family": "Kjellin", "given": "Hanna", "initials": "H"}, {"family": "Fotouhi", "given": "Omid", "initials": "O"}, {"family": "Lee", "given": "Linkiat", "initials": "L"}, {"family": "Nilsson", "given": "Inga-Lena", "initials": "IL"}, {"family": "Haglund", "given": "Felix", "initials": "F"}, {"family": "H\u00f6\u00f6g", "given": "Anders", "initials": "A"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Larsson", "given": "Catharina", "initials": "C"}], "type": "journal article", "published": "2018-07-15", "journal": {"volume": "470", "issn": "1872-8057", "issue": null, "title": "Mol. Cell. Endocrinol.", "pages": "84-95", "issn-l": "0303-7207"}, "abstract": "Parathyroid adenomas may be composed of chief cells (conventional or water-clear), oxyphilic cells or a mixture of both cells. The molecular background is rarely studied.\n\nTo molecularly characterize parathyroid adenomas of different cell type composition.\n\nChief and oxyphilic cell adenomas were compared in a cohort of 664 sporadic cases. Extensive analyses of parathyroid tissues were performed in subgroup. Gene expressions of known parathyroid-related genes were quantified by qRT-PCR. Protein expression profiles determined by liquid chromatography - tandem mass spectrometry (LC-MS/MS) were compared between each type of parathyroid adenomas. Selected proteins were analysed by Western blot and immunohistochemistry.\n\nPatients with oxyphilic cell adenoma were found to be older at the time of operation than chief cell adenoma cases but did not differ in gender, serum calcium or tumor weight. The gene expression of CASR, VDR, FGFR1, CYP27B1, CYP24A1, PTHLH, GCM2, NDUFA13, CDKN1B, MEN1 and CNND1 did not differ between the groups. VDR protein levels were weaker in oxyphilic adenomas. The proteomic studies identified a set of novel dysregulated proteins of interest such as nuclear receptor subfamily 2 group C member 2 (TR4), LIM domain only protein 3 (LMO3) and calcium-binding protein B (S100B). LMO3 and S100B showed higher expression in oxyphilic adenoma and may be involve in parathyroid tumorgenesis through the p53 pathway. TR4 showed different subcellular localisation between adenoma and normal rim.\n\nChief and oxyphilic cell parathyroid adenomas have partly overlapping but also distinct molecular profiles. The calmodulin-eEF2K, TR4 and p53 pathways may be involved in the tumor development.", "doi": "10.1016/j.mce.2017.10.001", "pmid": "28986304", "labels": {"Clinical Proteomics Mass spectrometry": "Service", "Global Proteomics and Proteogenomics": "Service"}, "xrefs": [{"db": "pii", "key": "S0303-7207(17)30521-X"}], "notes": [], "created": "2017-12-05T16:14:24.861Z", "modified": "2021-07-08T11:36:15.292Z"}, {"entity": "publication", "iuid": "c6cf18e2f5dd4881b77d08aa456280be", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c6cf18e2f5dd4881b77d08aa456280be.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c6cf18e2f5dd4881b77d08aa456280be"}}, "title": "A protein activity assay to measure global transcription factor activity reveals determinants of chromatin accessibility.", "authors": [{"family": "Wei", "given": "Bei", "initials": "B"}, {"family": "Jolma", "given": "Arttu", "initials": "A", "orcid": "0000-0002-2543-7490", "researcher": {"href": "https://publications.scilifelab.se/researcher/6beaa9e185a54934bddc490e7a8aa171.json"}}, {"family": "Sahu", "given": "Biswajyoti", "initials": "B"}, {"family": "Orre", "given": "Lukas M", "initials": "LM"}, {"family": "Zhong", "given": "Fan", "initials": "F"}, {"family": "Zhu", "given": "Fangjie", "initials": "F"}, {"family": "Kivioja", "given": "Teemu", "initials": "T"}, {"family": "Sur", "given": "Inderpreet", "initials": "I"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Taipale", "given": "Minna", "initials": "M"}, {"family": "Taipale", "given": "Jussi", "initials": "J"}], "type": "journal article", "published": "2018-07-00", "journal": {"volume": "36", "issn": "1546-1696", "issue": "6", "pages": "521-529", "title": "Nat. Biotechnol.", "issn-l": "1087-0156"}, "abstract": "No existing method to characterize transcription factor (TF) binding to DNA allows genome-wide measurement of all TF-binding activity in cells. Here we present a massively parallel protein activity assay, active TF identification (ATI), that measures the DNA-binding activity of all TFs in cell or tissue extracts. ATI is based on electrophoretic separation of protein-bound DNA sequences from a highly complex DNA library and subsequent mass-spectrometric identification of the DNA-bound proteins. We applied ATI to four mouse tissues and mouse embryonic stem cells and found that, in a given tissue or cell type, a small set of TFs, which bound to only \u223c10 distinct motifs, displayed strong DNA-binding activity. Some of these TFs were found in all cell types, whereas others were specific TFs known to determine cell fate in the analyzed tissue or cell type. We also show that a small number of TFs determined the accessible chromatin landscape of a cell, suggesting that gene regulatory logic may be simpler than previously appreciated.", "doi": "10.1038/nbt.4138", "pmid": "29786094", "labels": {"Global Proteomics and Proteogenomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "nbt.4138"}], "notes": [], "created": "2019-01-07T11:25:15.300Z", "modified": "2021-07-08T11:36:15.272Z"}, {"entity": "publication", "iuid": "72d2f199ac494d2c979b34f1c28aa30b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/72d2f199ac494d2c979b34f1c28aa30b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/72d2f199ac494d2c979b34f1c28aa30b"}}, "title": "Time-resolved transcriptome and proteome landscape of human regulatory T cell (Treg) differentiation reveals novel regulators of FOXP3.", "authors": [{"family": "Schmidt", "given": "Angelika", "initials": "A", "orcid": "0000-0002-1185-3012", "researcher": {"href": "https://publications.scilifelab.se/researcher/3708b225fbae4c239bdc3bea34beff17.json"}}, {"family": "Marabita", "given": "Francesco", "initials": "F"}, {"family": "Kiani", "given": "Narsis A", "initials": "NA"}, {"family": "Gross", "given": "Catharina C", "initials": "CC"}, {"family": "Johansson", "given": "Henrik J", "initials": "HJ"}, {"family": "\u00c9li\u00e1s", "given": "Szabolcs", "initials": "S"}, {"family": "Rautio", "given": "Sini", "initials": "S"}, {"family": "Eriksson", "given": "Matilda", "initials": "M"}, {"family": "Fernandes", "given": "Sunjay Jude", "initials": "SJ"}, {"family": "Silberberg", "given": "Gilad", "initials": "G"}, {"family": "Ullah", "given": "Ubaid", "initials": "U"}, {"family": "Bhatia", "given": "Urvashi", "initials": "U"}, {"family": "L\u00e4hdesm\u00e4ki", "given": "Harri", "initials": "H"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Gomez-Cabrero", "given": "David", "initials": "D"}, {"family": "Wiendl", "given": "Heinz", "initials": "H"}, {"family": "Lahesmaa", "given": "Riitta", "initials": "R"}, {"family": "Tegn\u00e9r", "given": "Jesper", "initials": "J"}], "type": "journal article", "published": "2018-05-07", "journal": {"volume": "16", "issn": "1741-7007", "issue": "1", "pages": "47", "title": "BMC Biol.", "issn-l": "1741-7007"}, "abstract": "Regulatory T cells (Tregs) expressing the transcription factor FOXP3 are crucial mediators of self-tolerance, preventing autoimmune diseases but possibly hampering tumor rejection. Clinical manipulation of Tregs is of great interest, and first-in-man trials of Treg transfer have achieved promising outcomes. Yet, the mechanisms governing induced Treg (iTreg) differentiation and the regulation of FOXP3 are incompletely understood.\n\nTo gain a comprehensive and unbiased molecular understanding of FOXP3 induction, we performed time-series RNA sequencing (RNA-Seq) and proteomics profiling on the same samples during human iTreg differentiation. To enable the broad analysis of universal FOXP3-inducing pathways, we used five differentiation protocols in parallel. Integrative analysis of the transcriptome and proteome confirmed involvement of specific molecular processes, as well as overlap of a novel iTreg subnetwork with known Treg regulators and autoimmunity-associated genes. Importantly, we propose 37 novel molecules putatively involved in iTreg differentiation. Their relevance was validated by a targeted shRNA screen confirming a functional role in FOXP3 induction, discriminant analyses classifying iTregs accordingly, and comparable expression in an independent novel iTreg RNA-Seq dataset.\n\nThe data generated by this novel approach facilitates understanding of the molecular mechanisms underlying iTreg generation as well as of the concomitant changes in the transcriptome and proteome. Our results provide a reference map exploitable for future discovery of markers and drug candidates governing control of Tregs, which has important implications for the treatment of cancer, autoimmune, and inflammatory diseases.", "doi": "10.1186/s12915-018-0518-3", "pmid": "29730990", "labels": {"Global Proteomics and Proteogenomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1186/s12915-018-0518-3"}, {"db": "pmc", "key": "PMC5937035"}], "notes": [], "created": "2019-01-07T11:35:26.403Z", "modified": "2021-07-08T11:36:15.231Z"}, {"entity": "publication", "iuid": "5c73c68928714d1ca470927905211c8e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5c73c68928714d1ca470927905211c8e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5c73c68928714d1ca470927905211c8e"}}, "title": "Discovery of coding regions in the human genome by integrated proteogenomics analysis workflow.", "authors": [{"family": "Zhu", "given": "Yafeng", "initials": "Y"}, {"family": "Orre", "given": "Lukas M", "initials": "LM"}, {"family": "Johansson", "given": "Henrik J", "initials": "HJ", "orcid": "0000-0003-4729-4205", "researcher": {"href": "https://publications.scilifelab.se/researcher/18aebf211fa640f48a7c8d860c168e5a.json"}}, {"family": "Huss", "given": "Mikael", "initials": "M"}, {"family": "Boekel", "given": "Jorrit", "initials": "J"}, {"family": "Vesterlund", "given": "Mattias", "initials": "M", "orcid": "0000-0001-9471-6592", "researcher": {"href": "https://publications.scilifelab.se/researcher/0942e438993b494db2a3db914852c808.json"}}, {"family": "Fernandez-Woodbridge", "given": "Alejandro", "initials": "A"}, {"family": "Branca", "given": "Rui M M", "initials": "RMM"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}], "type": "journal article", "published": "2018-03-02", "journal": {"volume": "9", "issn": "2041-1723", "issue": "1", "pages": "903", "title": "Nat Commun", "issn-l": "2041-1723"}, "abstract": "Proteogenomics enable the discovery of novel peptides (from unannotated genomic protein-coding loci) and single amino acid variant peptides (derived from single-nucleotide polymorphisms and mutations). Increasing the reliability of these identifications is crucial to ensure their usefulness for genome annotation and potential application as neoantigens in cancer immunotherapy. We here present integrated proteogenomics analysis workflow (IPAW), which combines peptide discovery, curation, and validation. IPAW includes the SpectrumAI tool for automated inspection of MS/MS spectra, eliminating false identifications of single-residue substitution peptides. We employ IPAW to analyze two proteomics data sets acquired from A431 cells and five normal human tissues using extended (pH range, 3-10) high-resolution isoelectric focusing (HiRIEF) pre-fractionation and TMT-based peptide quantitation. The IPAW results provide evidence for the translation of pseudogenes, lncRNAs, short ORFs, alternative ORFs, N-terminal extensions, and intronic sequences. Moreover, our quantitative analysis indicates that protein production from certain pseudogenes and lncRNAs is tissue specific.", "doi": "10.1038/s41467-018-03311-y", "pmid": "29500430", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Long-term Support WABI": "Collaborative", "Bioinformatics Support and Infrastructure": "Collaborative", "Global Proteomics and Proteogenomics": "Technology development", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-018-03311-y"}, {"db": "pmc", "key": "PMC5834625"}], "notes": [], "created": "2018-03-04T17:55:08.112Z", "modified": "2024-01-16T13:48:46.793Z"}, {"entity": "publication", "iuid": "91b082c53abd498c925f3a247ccd34ea", "links": {"self": {"href": "https://publications.scilifelab.se/publication/91b082c53abd498c925f3a247ccd34ea.json"}, "display": {"href": "https://publications.scilifelab.se/publication/91b082c53abd498c925f3a247ccd34ea"}}, "title": "MYCN-amplified neuroblastoma maintains an aggressive and undifferentiated phenotype by deregulation of estrogen and NGF signaling.", "authors": [{"family": "Dzieran", "given": "Johanna", "initials": "J"}, {"family": "Rodriguez Garcia", "given": "Aida", "initials": "A"}, {"family": "Westermark", "given": "Ulrica Kristina", "initials": "UK"}, {"family": "Henley", "given": "Aine Brigette", "initials": "AB"}, {"family": "Eyre S\u00e1nchez", "given": "Elena", "initials": "E"}, {"family": "Tr\u00e4ger", "given": "Catarina", "initials": "C"}, {"family": "Johansson", "given": "Henrik Johan", "initials": "HJ"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Arsenian-Henriksson", "given": "Marie", "initials": "M"}], "type": "journal article", "published": "2018-02-06", "journal": {"volume": "115", "issn": "1091-6490", "issue": "6", "pages": "E1229-E1238", "title": "Proc. Natl. Acad. Sci. U.S.A.", "issn-l": "0027-8424"}, "abstract": "Neuroblastoma (NB) is a remarkably heterogenic childhood tumor of the sympathetic nervous system with clinical behavior ranging from spontaneous regression to poorly differentiated tumors and metastasis. MYCN is amplified in 20% of cases and correlates with an undifferentiated, aggressive phenotype and poor prognosis. Estrogen receptor alpha (ER\u03b1) and the nerve growth factor (NGF) receptors TrkA and p75NTR are involved in neuronal differentiation and survival. We have previously shown that MYCN, via miR-18a, targets ER\u03b1 in NB cells. Here, we demonstrate that interference with miR-18a or overexpression of ER\u03b1 is sufficient to induce NGF signaling and to modulate both basal and NGF-induced neuronal differentiation in MYCN-amplified NB cells. Proteomic analysis confirmed an increase of neuronal features and showed that processes linked to tumor initiation and progression were inhibited upon ER\u03b1 overexpression. Indeed, ectopic ER\u03b1 expression was sufficient to inhibit metabolic activity and tumorigenic processes, including glycolysis, oxidative phosphorylation, cell viability, migration, and anchorage independent growth. Importantly, ER\u03b1 overexpression reduced tumor burden in NB mouse models and high ER\u03b1 levels were linked to improved survival in patients. In addition to ER\u03b1, several other nuclear hormone receptors (NHRs), including the glucocorticoid and the retinoic acid receptors, correlated with clinical markers for favorable and low-stage NB disease. Our data suggest that MYCN targets ER\u03b1 and thereby NGF signaling to maintain an undifferentiated and aggressive phenotype. Notably, we identified the estrogen-NGF crosstalk, as well as a set of other NHRs, as potential prognostic markers and targets for therapeutic strategies against NB.", "doi": "10.1073/pnas.1710901115", "pmid": "29374092", "labels": {"Global Proteomics and Proteogenomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "1710901115"}, {"db": "pmc", "key": "PMC5819392"}], "notes": [], "created": "2019-01-07T11:35:26.861Z", "modified": "2021-07-08T11:36:15.247Z"}, {"entity": "publication", "iuid": "ee6612f009784d75bef6f813135621b2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ee6612f009784d75bef6f813135621b2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ee6612f009784d75bef6f813135621b2"}}, "title": "A Common Peptidolytic Mechanism for Targeting Peptide Degradation in Mitochondria and Chloroplasts.", "authors": [{"family": "Kmiec", "given": "Beata", "initials": "B"}, {"family": "Branca", "given": "Rui M M", "initials": "RMM"}, {"family": "Murcha", "given": "Monika W", "initials": "MW"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Glaser", "given": "Elzbieta", "initials": "E"}, {"family": "Teixeira", "given": "Pedro F", "initials": "PF"}], "type": "letter", "published": "2018-02-05", "journal": {"title": "Mol Plant", "issn": "1752-9867", "issn-l": "1674-2052", "volume": "11", "issue": "2", "pages": "342-345"}, "abstract": null, "doi": "10.1016/j.molp.2017.11.008", "pmid": "29183773", "labels": {"Global Proteomics and Proteogenomics": "Service", "Clinical Proteomics Mass spectrometry": "Service", "Swedish Metabolomics Centre": "Service"}, "xrefs": [{"db": "pii", "key": "S1674-2052(17)30342-8"}], "notes": [], "created": "2018-10-31T07:12:33.028Z", "modified": "2025-10-17T13:03:18.311Z"}, {"entity": "publication", "iuid": "3c9517923fd04189a047817e54cbdc2f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3c9517923fd04189a047817e54cbdc2f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3c9517923fd04189a047817e54cbdc2f"}}, "title": "Mechanism of Peptide Binding and Cleavage by the Human Mitochondrial Peptidase Neurolysin.", "authors": [{"family": "Teixeira", "given": "Pedro F", "initials": "PF"}, {"family": "Masuyer", "given": "Geoffrey", "initials": "G"}, {"family": "Pinho", "given": "Catarina M", "initials": "CM"}, {"family": "Branca", "given": "Rui M M", "initials": "RMM"}, {"family": "Kmiec", "given": "Beata", "initials": "B"}, {"family": "Wallin", "given": "Cecilia", "initials": "C"}, {"family": "W\u00e4rml\u00e4nder", "given": "Sebastian K T S", "initials": "SKTS"}, {"family": "Berntsson", "given": "Ronnie P-A", "initials": "RP"}, {"family": "Ankarcrona", "given": "Maria", "initials": "M"}, {"family": "Gr\u00e4slund", "given": "Astrid", "initials": "A"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P"}, {"family": "Glaser", "given": "Elzbieta", "initials": "E"}], "type": "journal article", "published": "2018-02-02", "journal": {"volume": "430", "issn": "1089-8638", "issue": "3", "title": "J. Mol. Biol.", "pages": "348-362", "issn-l": "0022-2836"}, "abstract": "Proteolysis plays an important role in mitochondrial biogenesis, from the processing of newly imported precursor proteins to the degradation of mitochondrial targeting peptides. Disruption of peptide degradation activity in yeast, plant and mammalian mitochondria is known to have deleterious consequences for organism physiology, highlighting the important role of mitochondrial peptidases. In the present work, we show that the human mitochondrial peptidase neurolysin (hNLN) can degrade mitochondrial presequence peptides as well as other fragments up to 19 amino acids long. The crystal structure of hNLNE475Q in complex with the products of neurotensin cleavage at 2.7\u00c5 revealed a closed conformation with an internal cavity that restricts substrate length and highlighted the mechanism of enzyme opening/closing that is necessary for substrate binding and catalytic activity. Analysis of peptide degradation in vitro showed that hNLN cooperates with presequence protease (PreP or PITRM1) in the degradation of long targeting peptides and amyloid-\u03b2 peptide, A\u03b21-40, associated with Alzheimer disease, particularly cleaving the hydrophobic fragment A\u03b235-40. These findings suggest that a network of proteases may be required for complete degradation of peptides localized in mitochondria.", "doi": "10.1016/j.jmb.2017.11.011", "pmid": "29183787", "labels": {"Clinical Proteomics Mass spectrometry": "Service", "Global Proteomics and Proteogenomics": "Service"}, "xrefs": [{"db": "pii", "key": "S0022-2836(17)30561-2"}], "notes": [], "created": "2017-12-05T16:12:35.308Z", "modified": "2021-07-08T11:36:15.178Z"}, {"entity": "publication", "iuid": "a60b6a97c659488e90cccb7c10b92482", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a60b6a97c659488e90cccb7c10b92482.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a60b6a97c659488e90cccb7c10b92482"}}, "title": "Splicing of platelet resident pre-mRNAs upon activation by physiological stimuli results in functionally relevant proteome modifications.", "authors": [{"family": "Nassa", "given": "Giovanni", "initials": "G", "orcid": "0000-0001-7453-1240", "researcher": {"href": "https://publications.scilifelab.se/researcher/3c29044382c44e18a098f3825567f4fb.json"}}, {"family": "Giurato", "given": "Giorgio", "initials": "G"}, {"family": "Cimmino", "given": "Giovanni", "initials": "G"}, {"family": "Rizzo", "given": "Francesca", "initials": "F"}, {"family": "Ravo", "given": "Maria", "initials": "M"}, {"family": "Salvati", "given": "Annamaria", "initials": "A"}, {"family": "Nyman", "given": "Tuula A", "initials": "TA", "orcid": "0000-0001-8787-5886", "researcher": {"href": "https://publications.scilifelab.se/researcher/62a2a62d54ba4be2a5a747fbbfc5bcc3.json"}}, {"family": "Zhu", "given": "Yafeng", "initials": "Y"}, {"family": "Vesterlund", "given": "Mattias", "initials": "M", "orcid": "0000-0001-9471-6592", "researcher": {"href": "https://publications.scilifelab.se/researcher/0942e438993b494db2a3db914852c808.json"}}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Golino", "given": "Paolo", "initials": "P"}, {"family": "Weisz", "given": "Alessandro", "initials": "A"}, {"family": "Tarallo", "given": "Roberta", "initials": "R", "orcid": "0000-0001-9668-3632", "researcher": {"href": "https://publications.scilifelab.se/researcher/27138966f8b84f5d810aafa53a7e9304.json"}}], "type": "journal article", "published": "2018-01-11", "journal": {"volume": "8", "issn": "2045-2322", "issue": "1", "pages": "498", "title": "Sci Rep", "issn-l": "2045-2322"}, "abstract": "Platelet activation triggers thrombus formation in physiological and pathological conditions, such as acute coronary syndromes. Current therapies still fail to prevent thrombotic events in numerous patients, indicating that the mechanisms modulating platelet response during activation need to be clarified. The evidence that platelets are capable of de novo protein synthesis in response to stimuli raised the issue of how megakaryocyte-derived mRNAs are regulated in these anucleate cell fragments. Proteogenomics was applied here to investigate this phenomeon in platelets activated in vitro with Collagen or Thrombin Receptor Activating Peptide. Combining proteomics and transcriptomics allowed in depth platelet proteome characterization, revealing a significant effect of either stimulus on proteome composition. In silico analysis revealed the presence of resident immature RNAs in resting platelets, characterized by retained introns, while unbiased proteogenomics correlated intron removal by RNA splicing with changes on proteome composition upon activation. This allowed identification of a set of transcripts undergoing maturation by intron removal during activation and resulting in accumulation of the corresponding peptides at exon-exon junctions. These results indicate that RNA splicing events occur in platelets during activation and that maturation of specific pre-mRNAs is part of the activation cascade, contributing to a dynamic fine-tuning of the transcriptome.", "doi": "10.1038/s41598-017-18985-5", "pmid": "29323256", "labels": {"Global Proteomics and Proteogenomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-017-18985-5"}, {"db": "pmc", "key": "PMC5765118"}], "notes": [], "created": "2019-01-07T12:26:09.138Z", "modified": "2021-07-08T11:36:15.124Z"}, {"entity": "publication", "iuid": "f08e80cf3ad947d6b39ed822df64d201", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f08e80cf3ad947d6b39ed822df64d201.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f08e80cf3ad947d6b39ed822df64d201"}}, "title": "Normalization of mass spectrometry data (NOMAD).", "authors": [{"family": "Murie", "given": "Carl", "initials": "C"}, {"family": "Sandri", "given": "Brian", "initials": "B"}, {"family": "Sandberg", "given": "Ann-Sofi", "initials": "AS", "orcid": "0000-0002-9681-3342", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd34d8e107be4a87b60c8dc525277463.json"}}, {"family": "Griffin", "given": "Timothy J", "initials": "TJ"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Wendt", "given": "Christine", "initials": "C"}, {"family": "Larsson", "given": "Ola", "initials": "O"}], "type": "journal article", "published": "2018-01-00", "journal": {"volume": "67", "issn": "2212-4934", "issue": null, "title": "Adv Biol Regul", "pages": "128-133", "issn-l": "2212-4926"}, "abstract": "iTRAQ and TMT reagent-based mass spectrometry (MS) are commonly used technologies for quantitative proteomics in biological samples. Such studies are often performed over multiple MS runs, potentially resulting in introduction of MS run bias that could affect downstream analysis. Such MS data have therefore commonly been normalized using a reference sample which is included in each MS run. We show, however, that reference normalization does not effectively remove systematic MS run bias. A linear model approach was previously proposed to improve on the reference normalization approach but does not computationally scale to larger data sets. Here we describe the NOMAD (normalization of mass spectrometry data) R package which implements a computationally efficient ANOVA normalization approach with protein assembly functionality. NOMAD provides the same advantages as the linear regression solution but is more computationally efficient which allows superior scaling to larger sample sizes. Moreover, NOMAD effectively removes bias which improves valid across MS run comparisons.", "doi": "10.1016/j.jbior.2017.11.005", "pmid": "29174395", "labels": {"Clinical Proteomics Mass spectrometry": "Service", "Global Proteomics and Proteogenomics": "Service"}, "xrefs": [{"db": "pii", "key": "S2212-4926(17)30174-4"}, {"db": "pmc", "key": "PMC5885284"}, {"db": "mid", "key": "NIHMS951780"}], "notes": [], "created": "2017-12-05T16:14:22.060Z", "modified": "2023-06-19T12:54:45.273Z"}, {"entity": "publication", "iuid": "322d19d8a8f24583bfce02ae7f8a2aa2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/322d19d8a8f24583bfce02ae7f8a2aa2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/322d19d8a8f24583bfce02ae7f8a2aa2"}}, "title": "Female mice lacking Pald1 exhibit endothelial cell apoptosis and emphysema.", "authors": [{"family": "Ega\u00f1a", "given": "Isabel", "initials": "I"}, {"family": "Kaito", "given": "Hiroshi", "initials": "H"}, {"family": "Nitzsche", "given": "Anja", "initials": "A"}, {"family": "Becker", "given": "Lore", "initials": "L"}, {"family": "Ballester-Lopez", "given": "Carolina", "initials": "C"}, {"family": "Niaudet", "given": "Colin", "initials": "C"}, {"family": "Petkova", "given": "Milena", "initials": "M"}, {"family": "Liu", "given": "Wei", "initials": "W"}, {"family": "Vanlandewijck", "given": "Michael", "initials": "M"}, {"family": "Vernaleken", "given": "Alexandra", "initials": "A"}, {"family": "Klopstock", "given": "Thomas", "initials": "T"}, {"family": "Fuchs", "given": "Helmut", "initials": "H"}, {"family": "Gailus-Durner", "given": "Valerie", "initials": "V"}, {"family": "Hrabe de Angelis", "given": "Martin", "initials": "M"}, {"family": "Rask-Andersen", "given": "Helge", "initials": "H"}, {"family": "Johansson", "given": "Henrik J", "initials": "HJ"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "He", "given": "Liqun", "initials": "L"}, {"family": "Yildirim", "given": "Ali \u00d6", "initials": "A\u00d6"}, {"family": "Hellstr\u00f6m", "given": "Mats", "initials": "M"}, {"family": "German Mouse Clinic Consortium", "given": "", "initials": ""}], "type": "journal article", "published": "2017-11-13", "journal": {"volume": "7", "issn": "2045-2322", "issue": "1", "pages": "15453", "title": "Sci Rep", "issn-l": "2045-2322"}, "abstract": "Paladin (Pald1, mKIAA1274 or x99384) was identified in screens for vascular-specific genes and is a putative phosphatase. Paladin has also been proposed to be involved in various biological processes such as insulin signaling, innate immunity and neural crest migration. To determine the role of paladin we have now characterized the Pald1 knock-out mouse in a broad array of behavioral, physiological and biochemical tests. Here, we show that female, but not male, Pald1 heterozygous and homozygous knock-out mice display an emphysema-like histology with increased alveolar air spaces and impaired lung function with an obstructive phenotype. In contrast to many other tissues where Pald1 is restricted to the vascular compartment, Pald1 is expressed in both the epithelial and mesenchymal compartments of the postnatal lung. However, in Pald1 knock-out females, there is a specific increase in apoptosis and proliferation of endothelial cells, but not in non-endothelial cells. This results in a transient reduction of endothelial cells in the maturing lung. Our data suggests that Pald1 is required during lung vascular development and for normal function of the developing and adult lung in a sex-specific manner. To our knowledge, this is the first report of a sex-specific effect on endothelial cell apoptosis.", "doi": "10.1038/s41598-017-14894-9", "pmid": "29133847", "labels": {"Clinical Proteomics Mass spectrometry": "Service", "Global Proteomics and Proteogenomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-017-14894-9"}, {"db": "pmc", "key": "PMC5684320"}], "notes": [], "created": "2017-12-05T16:14:22.822Z", "modified": "2021-07-08T11:36:15.159Z"}, {"entity": "publication", "iuid": "60b0d98d513c4af988e4c92ae49decbd", "links": {"self": {"href": "https://publications.scilifelab.se/publication/60b0d98d513c4af988e4c92ae49decbd.json"}, "display": {"href": "https://publications.scilifelab.se/publication/60b0d98d513c4af988e4c92ae49decbd"}}, "title": "Identification of the PAK4 interactome reveals PAK4 phosphorylation of N-WASP and promotion of Arp2/3-dependent actin polymerization.", "authors": [{"family": "Zhao", "given": "Miao", "initials": "M"}, {"family": "Spiess", "given": "Matthias", "initials": "M"}, {"family": "Johansson", "given": "Henrik J", "initials": "HJ"}, {"family": "Olofsson", "given": "Helene", "initials": "H"}, {"family": "Hu", "given": "Jianjiang", "initials": "J"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Str\u00f6mblad", "given": "Staffan", "initials": "S"}], "type": "journal article", "published": "2017-09-29", "journal": {"volume": "8", "issn": "1949-2553", "issue": "44", "pages": "77061-77074", "title": "Oncotarget", "issn-l": "1949-2553"}, "abstract": "p21-activated kinase 4 (PAK4) regulates cell proliferation, apoptosis, cell motility and F-actin remodeling, but the PAK4 interactome has not been systematically analyzed. Here, we comprehensively characterized the human PAK4 interactome by iTRAQ quantitative mass spectrometry of PAK4-immunoprecipitations. Consistent with its multiple reported functions, the PAK4 interactome was enriched in diverse protein networks, including the 14-3-3, proteasome, replication fork, CCT and Arp2/3 complexes. Because PAK4 co-immunoprecipitated most subunits of the Arp2/3 complex, we hypothesized that PAK4 may play a role in Arp2/3 dependent actin regulation. Indeed, we found that PAK4 interacts with and phosphorylates the nucleation promoting factor N-WASP at Ser484/Ser485 and promotes Arp2/3-dependent actin polymerization in vitro. Also, PAK4 ablation in vivo reduced N-WASP Ser484/Ser485 phosphorylation and altered the cellular balance between G- and F-actin as well as the actin organization. By presenting the PAK4 interactome, we here provide a powerful resource for further investigations and as proof of principle, we also indicate a novel mechanism by which PAK4 regulates actin cytoskeleton remodeling.", "doi": "10.18632/oncotarget.20352", "pmid": "29100370", "labels": {"Clinical Proteomics Mass spectrometry": "Service", "Global Proteomics and Proteogenomics": "Service"}, "xrefs": [{"db": "pii", "key": "20352"}, {"db": "pmc", "key": "PMC5652764"}], "notes": [], "created": "2017-12-05T16:14:23.542Z", "modified": "2021-07-08T11:36:15.220Z"}, {"entity": "publication", "iuid": "d1e74ad1e3134682be2aa625c2c3d42f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d1e74ad1e3134682be2aa625c2c3d42f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d1e74ad1e3134682be2aa625c2c3d42f"}}, "title": "Tartrate-resistant acid phosphatase (TRAP/ACP5) promotes metastasis-related properties via TGF\u03b22/T\u03b2R and CD44 in MDA-MB-231 breast cancer cells.", "authors": [{"family": "Reithmeier", "given": "Anja", "initials": "A"}, {"family": "Panizza", "given": "Elena", "initials": "E"}, {"family": "Krumpel", "given": "Michael", "initials": "M"}, {"family": "Orre", "given": "Lukas M", "initials": "LM"}, {"family": "Branca", "given": "Rui M M", "initials": "RMM"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Ek-Rylander", "given": "Barbro", "initials": "B"}, {"family": "Andersson", "given": "G\u00f6ran", "initials": "G"}], "type": "journal article", "published": "2017-09-15", "journal": {"volume": "17", "issn": "1471-2407", "issue": "1", "pages": "650", "title": "BMC Cancer", "issn-l": "1471-2407"}, "abstract": "Tartrate-resistant acid phosphatase (TRAP/ACP5), a metalloenzyme that is characteristic for its expression in activated osteoclasts and in macrophages, has recently gained considerable focus as a driver of metastasis and was associated with clinically relevant parameters of cancer progression and cancer aggressiveness.\n\nMDA-MB-231 breast cancer cells with different TRAP expression levels (overexpression and knockdown) were generated and characterized for protein expression and activity levels. Functional cell experiments, such as proliferation, migration and invasion assays were performed as well as global phosphoproteomic and proteomic analysis was conducted to connect molecular perturbations to the phenotypic changes.\n\nWe identified an association between metastasis-related properties of TRAP-overexpressing MDA-MB-231 breast cancer cells and a TRAP-dependent regulation of Transforming growth factor (TGF\u03b2) pathway proteins and Cluster of differentiation 44 (CD44). Overexpression of TRAP increased anchorage-independent and anchorage-dependent cell growth and proliferation, induced a more elongated cellular morphology and promoted cell migration and invasion. Migration was increased in the presence of the extracellular matrix (ECM) proteins osteopontin and fibronectin and the basement membrane proteins collagen IV and laminin I. TRAP-induced properties were reverted upon shRNA-mediated knockdown of TRAP or treatment with the small molecule TRAP inhibitor 5-PNA. Global phosphoproteomics and proteomics analyses identified possible substrates of TRAP phosphatase activity or signaling intermediates and outlined a TRAP-dependent regulation of proteins involved in cell adhesion and ECM organization. Upregulation of TGF\u03b2 isoform 2 (TGF\u03b22), TGF\u03b2 receptor type 1 (T\u03b2R1) and Mothers against decapentaplegic homolog 2 (SMAD2), as well as increased intracellular phosphorylation of CD44 were identified upon TRAP perturbation. Functional antibody-mediated blocking and chemical inhibition demonstrated that TRAP-dependent migration and proliferation is regulated via TGF\u03b22/T\u03b2R, whereas proliferation beyond basal levels is regulated through CD44.\n\nAltogether, TRAP promotes metastasis-related cell properties in MDA-MB-231 breast cancer cells via TGF\u03b22/T\u03b2R and CD44, thereby identifying a potential signaling mechanism associated to TRAP action in breast cancer cells.", "doi": "10.1186/s12885-017-3616-7", "pmid": "28915803", "labels": {"Clinical Proteomics Mass spectrometry": "Service", "Global Proteomics and Proteogenomics": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s12885-017-3616-7"}, {"db": "pmc", "key": "PMC5602878"}], "notes": [], "created": "2017-12-05T16:14:25.657Z", "modified": "2021-07-08T11:36:15.281Z"}, {"entity": "publication", "iuid": "481f7584fddd4db2a5d9f3833a7ed7e8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/481f7584fddd4db2a5d9f3833a7ed7e8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/481f7584fddd4db2a5d9f3833a7ed7e8"}}, "title": "Silencing FLI or targeting CD13/ANPEP lead to dephosphorylation of EPHA2, a mediator of BRAF inhibitor resistance, and induce growth arrest or apoptosis in melanoma cells.", "authors": [{"family": "Azimi", "given": "Alireza", "initials": "A"}, {"family": "Tuominen", "given": "Rainer", "initials": "R"}, {"family": "Costa Svedman", "given": "Fernanda", "initials": "F"}, {"family": "Caramuta", "given": "Stefano", "initials": "S"}, {"family": "Pernemalm", "given": "Maria", "initials": "M", "orcid": "0000-0003-4624-031X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f15f303cb2044cfa81719700137e3603.json"}}, {"family": "Frostvik Stolt", "given": "Marianne", "initials": "M"}, {"family": "Kanter", "given": "Lena", "initials": "L"}, {"family": "Kharaziha", "given": "Pedram", "initials": "P"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Hertzman Johansson", "given": "Carolina", "initials": "C"}, {"family": "H\u00f6iom", "given": "Veronica", "initials": "V"}, {"family": "Hansson", "given": "Johan", "initials": "J"}, {"family": "Egyhazi Brage", "given": "Suzanne", "initials": "S", "orcid": "0000-0002-0524-2346", "researcher": {"href": "https://publications.scilifelab.se/researcher/40eddeacb66f490089dbf72978d20721.json"}}], "type": "journal article", "published": "2017-08-31", "journal": {"volume": "8", "issn": "2041-4889", "issue": "8", "pages": "e3029", "title": "Cell Death Dis", "issn-l": "2041-4889"}, "abstract": "A majority of patients with BRAF-mutated metastatic melanoma respond to therapy with BRAF inhibitors (BRAFi), but relapses are common owing to acquired resistance. To unravel BRAFi resistance mechanisms we have performed gene expression and mass spectrometry based proteome profiling of the sensitive parental A375 BRAF V600E-mutated human melanoma cell line and of daughter cell lines with induced BRAFi resistance. Increased expression of two novel resistance candidates, aminopeptidase-N (CD13/ANPEP) and ETS transcription factor FLI1 was observed in the BRAFi-resistant daughter cell lines. In addition, increased levels of the previously reported resistance mediators, receptor tyrosine kinase ephrine receptor A2 (EPHA2) and the hepatocyte growth factor receptor MET were also identified. The expression of these proteins was assessed in matched tumor samples from melanoma patients obtained before BRAFi and after disease progression. MET was overexpressed in all progression samples while the expression of the other candidates varied between the individual patients. Targeting CD13/ANPEP by a blocking antibody induced apoptosis in both parental A375- and BRAFi-resistant daughter cells as well as in melanoma cells with intrinsic BRAFi resistance and led to dephosphorylation of EPHA2 on S897, previously demonstrated to cause inhibition of the migratory capacity. AKT and RSK, both reported to induce EPHA2 S897 phosphorylation, were also dephosphorylated after inhibition of CD13/ANPEP. FLI1 silencing also caused decreases in EPHA2 S897 phosphorylation and in total MET protein expression. In addition, silencing of FLI1 sensitized the resistant cells to BRAFi. Furthermore, we show that BRAFi in combination with the multi kinase inhibitor dasatinib can abrogate BRAFi resistance and decrease both EPHA2 S897 phosphorylation and total FLI1 protein expression. This is the first report presenting CD13/ANPEP and FLI1 as important mediators of resistance to BRAF inhibition with potential as drug targets in BRAFi refractory melanoma.", "doi": "10.1038/cddis.2017.406", "pmid": "29048432", "labels": {"NGI Uppsala (Uppsala Genome Center)": "Service", "Clinical Proteomics Mass spectrometry": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "Global Proteomics and Proteogenomics": "Service"}, "xrefs": [{"db": "pii", "key": "cddis2017406"}, {"db": "pmc", "key": "PMC5596587"}], "notes": [], "created": "2017-10-17T07:53:20.719Z", "modified": "2021-07-08T11:36:54.639Z"}, {"entity": "publication", "iuid": "a782b516dd7b4b838b69f46f09a13e7d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a782b516dd7b4b838b69f46f09a13e7d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a782b516dd7b4b838b69f46f09a13e7d"}}, "title": "Tuning Metabolome Coverage in Reversed Phase LC-MS Metabolomics of MeOH Extracted Samples Using the Reconstitution Solvent Composition.", "authors": [{"family": "Lindahl", "given": "Anna", "initials": "A"}, {"family": "S\u00e4\u00e4f", "given": "Siv", "initials": "S"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Nordstr\u00f6m", "given": "Anders", "initials": "A", "orcid": "0000-0003-3676-817X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4b1803a3f7624f0d82abd552448bdaed.json"}}], "type": "journal article", "published": "2017-07-18", "journal": {"volume": "89", "issn": "1520-6882", "issue": "14", "pages": "7356-7364", "title": "Anal. Chem.", "issn-l": "0003-2700"}, "abstract": "Considering the physicochemical diversity of the metabolome, untargeted metabolomics will inevitably discriminate against certain compound classes. Efforts are nevertheless made to maximize the metabolome coverage. Contrary to the main steps of a typical liquid chromatography-mass spectrometry (LC-MS) metabolomics workflow, such as metabolite extraction, the sample reconstitution step has not been optimized for maximal metabolome coverage. This sample concentration step typically occurs after metabolite extraction, when dried samples are reconstituted in a solvent for injection on column. The aim of this study was to evaluate the impact of the sample reconstitution solvent composition on metabolome coverage in untargeted LC-MS metabolomics. Lysogeny Broth medium samples reconstituted in MeOH/H 2O ratios ranging from 0 to 100% MeOH and analyzed with untargeted reversed phase LC-MS showed that the highest number of metabolite features (n = 1500) was detected in samples reconstituted in 100% H2O. As compared to a commonly used reconstitution solvent mixture of 50/50 MeOH/H2O, our results indicate that the small fraction of compounds increasing in peak area response by the addition of MeOH to H2O, 5%, is outweighed by the fraction of compounds with decreased response, 57%. We evaluated our results on human serum samples from lymphoma patients and healthy control subjects. Reconstitution in 100% H2O resulted in a higher number of significant metabolites discriminating between these two groups than both 50% and 100% MeOH. These findings show that the sample reconstitution step has a clear impact on the metabolome coverage of MeOH extracted biological samples, highlighting the importance of the reconstitution solvent composition for untargeted discovery metabolomics.", "doi": "10.1021/acs.analchem.7b00475", "pmid": "28613827", "labels": {"Clinical Proteomics Mass spectrometry": "Service", "Global Proteomics and Proteogenomics": "Service", "Swedish Metabolomics Centre": "Technology development"}, "xrefs": [], "notes": [], "created": "2017-12-05T16:14:27.211Z", "modified": "2025-10-17T13:03:18.634Z"}, {"entity": "publication", "iuid": "44e0dcce999c41adb598ab8a38a2cc4c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/44e0dcce999c41adb598ab8a38a2cc4c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/44e0dcce999c41adb598ab8a38a2cc4c"}}, "title": "Isoelectric point-based fractionation by HiRIEF coupled to LC-MS allows for in-depth quantitative analysis of the phosphoproteome.", "authors": [{"family": "Panizza", "given": "Elena", "initials": "E"}, {"family": "Branca", "given": "Rui M M", "initials": "RMM"}, {"family": "Oliviusson", "given": "Peter", "initials": "P"}, {"family": "Orre", "given": "Lukas M", "initials": "LM"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}], "type": "journal article", "published": "2017-07-03", "journal": {"volume": "7", "issn": "2045-2322", "issue": "1", "pages": "4513", "title": "Sci Rep", "issn-l": "2045-2322"}, "abstract": "Protein phosphorylation is involved in the regulation of most eukaryotic cells functions and mass spectrometry-based analysis has made major contributions to our understanding of this regulation. However, low abundance of phosphorylated species presents a major challenge in achieving comprehensive phosphoproteome coverage and robust quantification. In this study, we developed a workflow employing titanium dioxide phospho-enrichment coupled with isobaric labeling by Tandem Mass Tags (TMT) and high-resolution isoelectric focusing (HiRIEF) fractionation to perform in-depth quantitative phosphoproteomics starting with a low sample quantity. To benchmark the workflow, we analyzed HeLa cells upon pervanadate treatment or cell cycle arrest in mitosis. Analyzing 300 \u00b5g of peptides per sample, we identified 22,712 phosphorylation sites, of which 19,075 were localized with high confidence and 1,203 are phosphorylated tyrosine residues, representing 6.3% of all detected phospho-sites. HiRIEF fractions with the most acidic isoelectric points are enriched in multiply phosphorylated peptides, which represent 18% of all the phospho-peptides detected in the pH range 2.5-3.7. Cross-referencing with the PhosphoSitePlus database reveals 1,264 phosphorylation sites that have not been previously reported and kinase association analysis suggests that a subset of these may be functional during the mitotic phase.", "doi": "10.1038/s41598-017-04798-z", "pmid": "28674419", "labels": {"Clinical Proteomics Mass spectrometry": "Service", "Global Proteomics and Proteogenomics": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-017-04798-z"}, {"db": "pmc", "key": "PMC5495806"}], "notes": [], "created": "2017-12-05T16:14:26.493Z", "modified": "2021-07-08T11:36:15.117Z"}, {"entity": "publication", "iuid": "99c4a012bd934c289bd13c457c63189a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/99c4a012bd934c289bd13c457c63189a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/99c4a012bd934c289bd13c457c63189a"}}, "title": "Discrimination of pancreatic cancer and pancreatitis by LC-MS metabolomics.", "authors": [{"family": "Lindahl", "given": "Anna", "initials": "A"}, {"family": "Heuchel", "given": "Rainer", "initials": "R"}, {"family": "Forshed", "given": "Jenny", "initials": "J"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "L\u00f6hr", "given": "Matthias", "initials": "M"}, {"family": "Nordstr\u00f6m", "given": "Anders", "initials": "A", "orcid": "0000-0003-3676-817X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4b1803a3f7624f0d82abd552448bdaed.json"}}], "type": "journal article", "published": "2017-04-01", "journal": {"volume": "13", "issn": "1573-3882", "issue": "5", "pages": "61", "title": "Metabolomics", "issn-l": null}, "abstract": "Pancreatic ductal adenocarcinoma (PDAC) is the fifth most common cause of cancer-related death in Europe with a 5-year survival rate of <5%. Chronic pancreatitis (CP) is a risk factor for PDAC development, but in the majority of cases malignancy is discovered too late for curative treatment. There is at present no reliable diagnostic marker for PDAC available.\n\nThe aim of the study was to identify single blood-based metabolites or a panel of metabolites discriminating PDAC and CP using liquid chromatography-mass spectrometry (LC-MS).\n\nA discovery cohort comprising PDAC (n = 44) and CP (n = 23) samples was analyzed by LC-MS followed by univariate (Student's t test) and multivariate (orthogonal partial least squares-discriminant analysis (OPLS-DA)) statistics. Discriminative metabolite features were subject to raw data examination and identification to ensure high feature quality. Their discriminatory power was then confirmed in an independent validation cohort including PDAC (n = 20) and CP (n = 31) samples.\n\nGlycocholic acid, N-palmitoyl glutamic acid and hexanoylcarnitine were identified as single markers discriminating PDAC and CP by univariate analysis. OPLS-DA resulted in a panel of five metabolites including the aforementioned three metabolites as well as phenylacetylglutamine (PAGN) and chenodeoxyglycocholate.\n\nUsing LC-MS-based metabolomics we identified three single metabolites and a five-metabolite panel discriminating PDAC and CP in two independent cohorts. Although further study is needed in larger cohorts, the metabolites identified are potentially of use in PDAC diagnostics.", "doi": "10.1007/s11306-017-1199-6", "pmid": "28413374", "labels": {"Clinical Proteomics Mass spectrometry": "Service", "Global Proteomics and Proteogenomics": "Service", "Swedish Metabolomics Centre": "Service"}, "xrefs": [{"db": "pii", "key": "1199"}, {"db": "pmc", "key": "PMC5376388"}], "notes": [], "created": "2017-12-05T16:14:27.928Z", "modified": "2025-10-17T13:03:18.911Z"}, {"entity": "publication", "iuid": "462837a655434c04a22ffd076f56c646", "links": {"self": {"href": "https://publications.scilifelab.se/publication/462837a655434c04a22ffd076f56c646.json"}, "display": {"href": "https://publications.scilifelab.se/publication/462837a655434c04a22ffd076f56c646"}}, "title": "Proteogenomics produces comprehensive and highly accurate protein-coding gene annotation in a complete genome assembly of Malassezia sympodialis.", "authors": [{"family": "Zhu", "given": "Yafeng", "initials": "Y", "orcid": "0000-0003-1947-9026", "researcher": {"href": "https://publications.scilifelab.se/researcher/d464b30bf5174a8fb456601d75aecb14.json"}}, {"family": "Engstr\u00f6m", "given": "P\u00e4r G", "initials": "PG", "orcid": "0000-0001-5265-2121", "researcher": {"href": "https://publications.scilifelab.se/researcher/0ce330ec225f4a8595932d092ab8c8d1.json"}}, {"family": "Tellgren-Roth", "given": "Christian", "initials": "C"}, {"family": "Baudo", "given": "Charles D", "initials": "CD"}, {"family": "Kennell", "given": "John C", "initials": "JC"}, {"family": "Sun", "given": "Sheng", "initials": "S"}, {"family": "Billmyre", "given": "R Blake", "initials": "RB"}, {"family": "Schr\u00f6der", "given": "Markus S", "initials": "MS"}, {"family": "Andersson", "given": "Anna", "initials": "A"}, {"family": "Holm", "given": "Tina", "initials": "T"}, {"family": "Sigurgeirsson", "given": "Benjamin", "initials": "B"}, {"family": "Wu", "given": "Guangxi", "initials": "G"}, {"family": "Sankaranarayanan", "given": "Sundar Ram", "initials": "SR"}, {"family": "Siddharthan", "given": "Rahul", "initials": "R"}, {"family": "Sanyal", "given": "Kaustuv", "initials": "K"}, {"family": "Lundeberg", "given": "Joakim", "initials": "J", "orcid": "0000-0003-4313-1601", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a4e6ca0f29b4ead8569e2729481c3e0.json"}}, {"family": "Nystedt", "given": "Bj\u00f6rn", "initials": "B", "orcid": "0000-0001-7809-7664", "researcher": {"href": "https://publications.scilifelab.se/researcher/f0af5a168baa4b00a6fab8d3447ebfb4.json"}}, {"family": "Boekhout", "given": "Teun", "initials": "T"}, {"family": "Dawson", "given": "Thomas L", "initials": "TL"}, {"family": "Heitman", "given": "Joseph", "initials": "J"}, {"family": "Scheynius", "given": "Annika", "initials": "A"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}], "type": "journal article", "published": "2017-03-17", "journal": {"volume": "45", "issn": "1362-4962", "issue": "5", "pages": "2629-2643", "title": "Nucleic Acids Res.", "issn-l": "0305-1048"}, "abstract": "Complete and accurate genome assembly and annotation is a crucial foundation for comparative and functional genomics. Despite this, few complete eukaryotic genomes are available, and genome annotation remains a major challenge. Here, we present a complete genome assembly of the skin commensal yeast Malassezia sympodialis and demonstrate how proteogenomics can substantially improve gene annotation. Through long-read DNA sequencing, we obtained a gap-free genome assembly for M. sympodialis (ATCC 42132), comprising eight nuclear and one mitochondrial chromosome. We also sequenced and assembled four M. sympodialis clinical isolates, and showed their value for understanding Malassezia reproduction by confirming four alternative allele combinations at the two mating-type loci. Importantly, we demonstrated how proteomics data could be readily integrated with transcriptomics data in standard annotation tools. This increased the number of annotated protein-coding genes by 14% (from 3612 to 4113), compared to using transcriptomics evidence alone. Manual curation further increased the number of protein-coding genes by 9% (to 4493). All of these genes have RNA-seq evidence and 87% were confirmed by proteomics. The M. sympodialis genome assembly and annotation presented here is at a quality yet achieved only for a few eukaryotic organisms, and constitutes an important reference for future host-microbe interaction studies.", "doi": "10.1093/nar/gkx006", "pmid": "28100699", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Long-term Support WABI": "Collaborative", "NGI Uppsala (Uppsala Genome Center)": "Collaborative", "Clinical Proteomics Mass spectrometry": "Technology development", "National Genomics Infrastructure": "Collaborative", "Global Proteomics and Proteogenomics": "Technology development", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "gkx006"}, {"db": "pmc", "key": "PMC5389616"}], "notes": [], "created": "2017-08-23T14:28:34.856Z", "modified": "2024-01-16T13:48:48.270Z"}, {"entity": "publication", "iuid": "37442ab98d914bb1827ce6b803dae200", "links": {"self": {"href": "https://publications.scilifelab.se/publication/37442ab98d914bb1827ce6b803dae200.json"}, "display": {"href": "https://publications.scilifelab.se/publication/37442ab98d914bb1827ce6b803dae200"}}, "title": "A multi-step peptidolytic cascade for amino acid recovery in chloroplasts.", "authors": [{"family": "Teixeira", "given": "Pedro F", "initials": "PF", "orcid": "0000-0001-8638-7477", "researcher": {"href": "https://publications.scilifelab.se/researcher/9b43730fe20b424db84f091333be7244.json"}}, {"family": "Kmiec", "given": "Beata", "initials": "B"}, {"family": "Branca", "given": "Rui M M", "initials": "RM"}, {"family": "Murcha", "given": "Monika W", "initials": "MW", "orcid": "0000-0002-3689-6158", "researcher": {"href": "https://publications.scilifelab.se/researcher/49b1e7e1fca74be090072ad2185c9827.json"}}, {"family": "Byzia", "given": "Anna", "initials": "A"}, {"family": "Ivanova", "given": "Aneta", "initials": "A"}, {"family": "Whelan", "given": "James", "initials": "J"}, {"family": "Drag", "given": "Marcin", "initials": "M"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Glaser", "given": "Elzbieta", "initials": "E"}], "type": "journal article", "published": "2017-01-00", "journal": {"volume": "13", "issn": "1552-4469", "issue": "1", "pages": "15-17", "title": "Nat. Chem. Biol.", "issn-l": "1552-4450"}, "abstract": "Plastids (including chloroplasts) are subcellular sites for a plethora of proteolytic reactions, required in functions ranging from protein biogenesis to quality control. Here we show that peptides generated from pre-protein maturation within chloroplasts of Arabidopsis thaliana are degraded to amino acids by a multi-step peptidolytic cascade consisting of oligopeptidases and aminopeptidases, effectively allowing the recovery of single amino acids within these organelles.", "doi": "10.1038/nchembio.2227", "pmid": "27820795", "labels": {"Clinical Proteomics Mass spectrometry": "Collaborative", "Global Proteomics and Proteogenomics": "Collaborative", "Swedish Metabolomics Centre": "Service"}, "xrefs": [{"db": "pii", "key": "nchembio.2227"}], "notes": [], "created": "2017-05-03T12:59:39.078Z", "modified": "2025-10-17T13:03:19.180Z"}, {"entity": "publication", "iuid": "f0189e06f40849b6aa396efe9d60aad1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f0189e06f40849b6aa396efe9d60aad1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f0189e06f40849b6aa396efe9d60aad1"}}, "title": "Validation and development of MTH1 inhibitors for treatment of cancer.", "authors": [{"family": "Warpman Berglund", "given": "U", "initials": "U"}, {"family": "Sanjiv", "given": "K", "initials": "K"}, {"family": "Gad", "given": "H", "initials": "H"}, {"family": "Kalder\u00e9n", "given": "C", "initials": "C"}, {"family": "Koolmeister", "given": "T", "initials": "T"}, {"family": "Pham", "given": "T", "initials": "T"}, {"family": "Gokturk", "given": "C", "initials": "C"}, {"family": "Jafari", "given": "R", "initials": "R"}, {"family": "Maddalo", "given": "G", "initials": "G"}, {"family": "Seashore-Ludlow", "given": "B", "initials": "B"}, {"family": "Chernobrovkin", "given": "A", "initials": "A"}, {"family": "Manoilov", "given": "A", "initials": "A"}, {"family": "Pateras", "given": "I S", "initials": "IS"}, {"family": "Rasti", "given": "A", "initials": "A"}, {"family": "Jemth", "given": "A-S", "initials": "AS"}, {"family": "Alml\u00f6f", "given": "I", "initials": "I"}, {"family": "Loseva", "given": "O", "initials": "O"}, {"family": "Visnes", "given": "T", "initials": "T"}, {"family": "Einarsdottir", "given": "B O", "initials": "BO"}, {"family": "Gaugaz", "given": "F Z", "initials": "FZ"}, {"family": "Saleh", "given": "A", "initials": "A"}, {"family": "Platzack", "given": "B", "initials": "B"}, {"family": "Wallner", "given": "O A", "initials": "OA"}, {"family": "Vallin", "given": "K S A", "initials": "KS"}, {"family": "Henriksson", "given": "M", "initials": "M"}, {"family": "Wakchaure", "given": "P", "initials": "P"}, {"family": "Borhade", "given": "S", "initials": "S"}, {"family": "Herr", "given": "P", "initials": "P"}, {"family": "Kallberg", "given": "Y", "initials": "Y"}, {"family": "Baranczewski", "given": "P", "initials": "P"}, {"family": "Homan", "given": "E J", "initials": "EJ"}, {"family": "Wiita", "given": "E", "initials": "E"}, {"family": "Nagpal", "given": "V", "initials": "V"}, {"family": "Meijer", "given": "T", "initials": "T"}, {"family": "Schipper", "given": "N", "initials": "N"}, {"family": "Rudd", "given": "S G", "initials": "SG"}, {"family": "Br\u00e4utigam", "given": "L", "initials": "L"}, {"family": "Lindqvist", "given": "A", "initials": "A"}, {"family": "Filppula", "given": "A", "initials": "A"}, {"family": "Lee", "given": "T-C", "initials": "TC"}, {"family": "Artursson", "given": "P", "initials": "P"}, {"family": "Nilsson", "given": "J A", "initials": "JA"}, {"family": "Gorgoulis", "given": "V G", "initials": "VG"}, {"family": "Lehti\u00f6", "given": "J", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Zubarev", "given": "R A", "initials": "RA", "orcid": "0000-0001-9839-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/e971b9cdec2b4411934f9c5d535da8b4.json"}}, {"family": "Scobie", "given": "M", "initials": "M"}, {"family": "Helleday", "given": "T", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7256c271ea4adea404d4ff355f804e.json"}}], "type": "journal article", "published": "2016-12-00", "journal": {"volume": "27", "issn": "1569-8041", "issue": "12", "pages": "2275-2283", "title": "Ann. Oncol.", "issn-l": "0923-7534"}, "abstract": "Previously, we showed cancer cells rely on the MTH1 protein to prevent incorporation of otherwise deadly oxidised nucleotides into DNA and we developed MTH1 inhibitors which selectively kill cancer cells. Recently, several new and potent inhibitors of MTH1 were demonstrated to be non-toxic to cancer cells, challenging the utility of MTH1 inhibition as a target for cancer treatment.\n\nHuman cancer cell lines were exposed in vitro to MTH1 inhibitors or depleted of MTH1 by siRNA or shRNA. 8-oxodG was measured by immunostaining and modified comet assay. Thermal Proteome profiling, proteomics, cellular thermal shift assays, kinase and CEREP panel were used for target engagement, mode of action and selectivity investigations of MTH1 inhibitors. Effect of MTH1 inhibition on tumour growth was explored in BRAF V600E-mutated malignant melanoma patient derived xenograft and human colon cancer SW480 and HCT116 xenograft models.\n\nHere, we demonstrate that recently described MTH1 inhibitors, which fail to kill cancer cells, also fail to introduce the toxic oxidized nucleotides into DNA. We also describe a new MTH1 inhibitor TH1579, (Karonudib), an analogue of TH588, which is a potent, selective MTH1 inhibitor with good oral availability and demonstrates excellent pharmacokinetic and anti-cancer properties in vivo.\n\nWe demonstrate that in order to kill cancer cells MTH1 inhibitors must also introduce oxidized nucleotides into DNA. Furthermore, we describe TH1579 as a best-in-class MTH1 inhibitor, which we expect to be useful in order to further validate the MTH1 inhibitor concept.", "doi": "10.1093/annonc/mdw429", "pmid": "27827301", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Clinical Proteomics Mass spectrometry": "Collaborative", "Chemical Proteomics": "Service", "Advanced Mass Spectrometry Proteomics": "Collaborative", "Bioinformatics Support and Infrastructure": "Collaborative", "Bioinformatics (NBIS)": "Collaborative", "Chemical Biology Consortium Sweden": "Collaborative", "Drug Discovery and Development": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S0923-7534(19)36552-4"}], "notes": "Laboratories for Chemical Biology at Karolinska Institutet (LCBKI)\r\nADME of Therapeutics (UDOPP)", "created": "2017-05-03T12:58:49.192Z", "modified": "2025-10-17T13:05:09.110Z"}, {"entity": "publication", "iuid": "4f90bb3bf07a4fe28c6fd66458e7aa15", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4f90bb3bf07a4fe28c6fd66458e7aa15.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4f90bb3bf07a4fe28c6fd66458e7aa15"}}, "title": "Mesenchymal state of intimal cells may explain higher propensity to ascending aortic aneurysm in bicuspid aortic valves.", "authors": [{"family": "Maleki", "given": "Shohreh", "initials": "S"}, {"family": "Kjellqvist", "given": "Sanela", "initials": "S"}, {"family": "Paloschi", "given": "Valentina", "initials": "V"}, {"family": "Magn\u00e9", "given": "Joelle", "initials": "J"}, {"family": "Branca", "given": "Rui Miguel Mamede", "initials": "RM"}, {"family": "Du", "given": "Lei", "initials": "L"}, {"family": "Hultenby", "given": "Kjell", "initials": "K"}, {"family": "Petrini", "given": "Johan", "initials": "J"}, {"family": "Fuxe", "given": "Jonas", "initials": "J"}, {"family": "MIBAVA Leducq Consortium", "given": "", "initials": ""}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Franco-Cereceda", "given": "Anders", "initials": "A"}, {"family": "Eriksson", "given": "Per", "initials": "P"}, {"family": "Bj\u00f6rck", "given": "Hanna M", "initials": "HM"}], "type": "journal article", "published": "2016-10-25", "journal": {"volume": "6", "issn": "2045-2322", "issue": null, "pages": "35712", "title": "Sci Rep", "issn-l": "2045-2322"}, "abstract": "Individuals with a bicuspid aortic valve (BAV) are at significantly higher risk of developing aortic complications than individuals with tricuspid aortic valves (TAV) and defective signaling during the embryonic development and/or life time exposure to abnormal hemodynamic have been proposed as underlying factors. However, an explanation for the molecular mechanisms of aortopathy in BAV has not yet been provided. We combined proteomics, RNA analyses, immunohistochemistry, and electron microscopy to identify molecular differences in samples of non-dilated ascending aortas from BAV (N = 62) and TAV (N = 54) patients. Proteomic analysis was also performed for dilated aortas (N = 6 BAV and N = 5 TAV) to gain further insight into the aortopathy of BAV. Our results collectively showed the molecular signature of an endothelial/epithelial-mesenchymal (EndMT/EMT) transition-like process, associated with instability of intimal cell junctions and activation of RHOA pathway in the intima and media layers of ascending aorta in BAV patients. We propose that an improper regulation of EndMT/EMT during the spatiotemporally related embryogenesis of semilunar valves and ascending aorta in BAV individuals may result in aortic immaturity and instability prior to dilation. Exasperation of EndMT/EMT state in post embryonic life and/or exposure to non-physiological hemodynamic could lead to the aneurysm of ascending aorta in BAV individuals.", "doi": "10.1038/srep35712", "pmid": "27779199", "labels": {"Clinical Proteomics Mass spectrometry": "Collaborative", "Global Proteomics and Proteogenomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "srep35712"}, {"db": "pmc", "key": "PMC5078843"}], "notes": [], "created": "2017-05-03T13:02:33.158Z", "modified": "2021-07-08T11:36:15.208Z"}, {"entity": "publication", "iuid": "2d1e0d8777f14467b95be4fa850cb8a6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2d1e0d8777f14467b95be4fa850cb8a6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2d1e0d8777f14467b95be4fa850cb8a6"}}, "title": "Phenotypic Modulation of Smooth Muscle Cells in Atherosclerosis Is Associated With Downregulation of LMOD1, SYNPO2, PDLIM7, PLN, and SYNM.", "authors": [{"family": "Perisic Matic", "given": "Ljubica", "initials": "L"}, {"family": "Rykaczewska", "given": "Urszula", "initials": "U"}, {"family": "Razuvaev", "given": "Anton", "initials": "A"}, {"family": "Sabater-Lleal", "given": "Maria", "initials": "M"}, {"family": "Lengquist", "given": "Mariette", "initials": "M"}, {"family": "Miller", "given": "Clint L", "initials": "CL"}, {"family": "Ericsson", "given": "Ida", "initials": "I"}, {"family": "R\u00f6hl", "given": "Samuel", "initials": "S"}, {"family": "Kronqvist", "given": "Malin", "initials": "M"}, {"family": "Aldi", "given": "Silvia", "initials": "S"}, {"family": "Magn\u00e9", "given": "Joelle", "initials": "J"}, {"family": "Paloschi", "given": "Valentina", "initials": "V"}, {"family": "Vesterlund", "given": "Mattias", "initials": "M"}, {"family": "Li", "given": "Yuhuang", "initials": "Y"}, {"family": "Jin", "given": "Hong", "initials": "H"}, {"family": "Diez", "given": "Maria Gonzalez", "initials": "MG"}, {"family": "Roy", "given": "Joy", "initials": "J"}, {"family": "Baldassarre", "given": "Damiano", "initials": "D"}, {"family": "Veglia", "given": "Fabrizio", "initials": "F"}, {"family": "Humphries", "given": "Steve E", "initials": "SE"}, {"family": "de Faire", "given": "Ulf", "initials": "U"}, {"family": "Tremoli", "given": "Elena", "initials": "E"}, {"family": "Odeberg", "given": "Jacob", "initials": "J"}, {"family": "Vukojevi\u0107", "given": "Vladana", "initials": "V"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Maegdefessel", "given": "Lars", "initials": "L"}, {"family": "Ehrenborg", "given": "Ewa", "initials": "E"}, {"family": "Paulsson-Berne", "given": "Gabrielle", "initials": "G"}, {"family": "Hansson", "given": "G\u00f6ran K", "initials": "GK"}, {"family": "Lindeman", "given": "Jan H N", "initials": "JH"}, {"family": "Eriksson", "given": "Per", "initials": "P"}, {"family": "Quertermous", "given": "Thomas", "initials": "T"}, {"family": "Hamsten", "given": "Anders", "initials": "A"}, {"family": "Hedin", "given": "Ulf", "initials": "U"}], "type": "journal article", "published": "2016-09-00", "journal": {"volume": "36", "issn": "1524-4636", "issue": "9", "pages": "1947-1961", "title": "Arterioscler. Thromb. Vasc. Biol.", "issn-l": "1079-5642"}, "abstract": "Key augmented processes in atherosclerosis have been identified, whereas less is known about downregulated pathways. Here, we applied a systems biology approach to examine suppressed molecular signatures, with the hypothesis that they may provide insight into mechanisms contributing to plaque stability.\n\nMuscle contraction, muscle development, and actin cytoskeleton were the most downregulated pathways (false discovery rate=6.99e-21, 1.66e-6, 2.54e-10, respectively) in microarrays from human carotid plaques (n=177) versus healthy arteries (n=15). In addition to typical smooth muscle cell (SMC) markers, these pathways also encompassed cytoskeleton-related genes previously not associated with atherosclerosis. SYNPO2, SYNM, LMOD1, PDLIM7, and PLN expression positively correlated to typical SMC markers in plaques (Pearson r>0.6, P<0.0001) and in rat intimal hyperplasia (r>0.8, P<0.0001). By immunohistochemistry, the proteins were expressed in SMCs in normal vessels, but largely absent in human plaques and intimal hyperplasia. Subcellularly, most proteins localized to the cytoskeleton in cultured SMCs and were regulated by active enhancer histone modification H3K27ac by chromatin immunoprecipitation-sequencing. Functionally, the genes were downregulated by PDGFB (platelet-derived growth factor beta) and IFNg (interferron gamma), exposure to shear flow stress, and oxLDL (oxidized low-density lipoprotein) loading. Genetic variants in PDLIM7, PLN, and SYNPO2 loci associated with progression of carotid intima-media thickness in high-risk subjects without symptoms of cardiovascular disease (n=3378). By eQTL (expression quantitative trait locus), rs11746443 also associated with PDLIM7 expression in plaques. Mechanistically, silencing of PDLIM7 in vitro led to downregulation of SMC markers and disruption of the actin cytoskeleton, decreased cell spreading, and increased proliferation.\n\nWe identified a panel of genes that reflect the altered phenotype of SMCs in vascular disease and could be early sensitive markers of SMC dedifferentiation.", "doi": "10.1161/ATVBAHA.116.307893", "pmid": "27470516", "labels": {"Clinical Proteomics Mass spectrometry": "Collaborative", "Global Proteomics and Proteogenomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "ATVBAHA.116.307893"}], "notes": [], "created": "2017-05-03T13:02:33.883Z", "modified": "2021-07-08T11:36:15.145Z"}, {"entity": "publication", "iuid": "7d3a9a83444049e8b4d26652d57f1ad6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7d3a9a83444049e8b4d26652d57f1ad6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7d3a9a83444049e8b4d26652d57f1ad6"}}, "title": "Single base resolution analysis of 5-hydroxymethylcytosine in 188 human genes: implications for hepatic gene expression.", "authors": [{"family": "Ivanov", "given": "Maxim", "initials": "M"}, {"family": "Kals", "given": "Mart", "initials": "M"}, {"family": "Lauschke", "given": "Volker", "initials": "V"}, {"family": "Barragan", "given": "Isabel", "initials": "I"}, {"family": "Ewels", "given": "Philip", "initials": "P"}, {"family": "K\u00e4ller", "given": "Max", "initials": "M", "orcid": "0000-0001-6813-3051", "researcher": {"href": "https://publications.scilifelab.se/researcher/536ad902a272482aba853c078557e240.json"}}, {"family": "Axelsson", "given": "Tomas", "initials": "T"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Milani", "given": "Lili", "initials": "L"}, {"family": "Ingelman-Sundberg", "given": "Magnus", "initials": "M"}], "type": "journal article", "published": "2016-08-19", "journal": {"volume": "44", "issn": "1362-4962", "issue": "14", "pages": "6756-6769", "title": "Nucleic Acids Res.", "issn-l": "0305-1048"}, "abstract": "To improve the epigenomic analysis of tissues rich in 5-hydroxymethylcytosine (hmC), we developed a novel protocol called TAB-Methyl-SEQ, which allows for single base resolution profiling of both hmC and 5-methylcytosine by targeted next-generation sequencing. TAB-Methyl-SEQ data were extensively validated by a set of five methodologically different protocols. Importantly, these extensive cross-comparisons revealed that protocols based on Tet1-assisted bisulfite conversion provided more precise hmC values than TrueMethyl-based methods. A total of 109 454 CpG sites were analyzed by TAB-Methyl-SEQ for mC and hmC in 188 genes from 20 different adult human livers. We describe three types of variability of hepatic hmC profiles: (i) sample-specific variability at 40.8% of CpG sites analyzed, where the local hmC values correlate to the global hmC content of livers (measured by LC-MS), (ii) gene-specific variability, where hmC levels in the coding regions positively correlate to expression of the respective gene and (iii) site-specific variability, where prominent hmC peaks span only 1 to 3 neighboring CpG sites. Our data suggest that both the gene- and site-specific components of hmC variability might contribute to the epigenetic control of hepatic genes. The protocol described here should be useful for targeted DNA analysis in a variety of applications.", "doi": "10.1093/nar/gkw316", "pmid": "27131363", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Collaborative", "Clinical Proteomics Mass spectrometry": "Collaborative", "NGI Stockholm (Genomics Applications)": "Collaborative", "NGI Stockholm (Genomics Production)": "Collaborative", "National Genomics Infrastructure": "Collaborative", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "gkw316"}, {"db": "pmc", "key": "PMC5001587"}], "notes": [], "created": "2017-05-03T13:00:08.926Z", "modified": "2024-01-16T13:48:49.630Z"}, {"entity": "publication", "iuid": "cfe4260e16314a9ea8a28ff73a6111df", "links": {"self": {"href": "https://publications.scilifelab.se/publication/cfe4260e16314a9ea8a28ff73a6111df.json"}, "display": {"href": "https://publications.scilifelab.se/publication/cfe4260e16314a9ea8a28ff73a6111df"}}, "title": "Cells release subpopulations of exosomes with distinct molecular and biological properties.", "authors": [{"family": "Willms", "given": "Eduard", "initials": "E"}, {"family": "Johansson", "given": "Henrik J", "initials": "HJ"}, {"family": "M\u00e4ger", "given": "Imre", "initials": "I"}, {"family": "Lee", "given": "Yi", "initials": "Y"}, {"family": "Blomberg", "given": "K Emelie M", "initials": "KE"}, {"family": "Sadik", "given": "Mariam", "initials": "M"}, {"family": "Alaarg", "given": "Amr", "initials": "A"}, {"family": "Smith", "given": "C I Edvard", "initials": "CI"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "El Andaloussi", "given": "Samir", "initials": "S"}, {"family": "Wood", "given": "Matthew J A", "initials": "MJ"}, {"family": "Vader", "given": "Pieter", "initials": "P"}], "type": "journal article", "published": "2016-03-02", "journal": {"volume": "6", "issn": "2045-2322", "issue": null, "pages": "22519", "title": "Sci Rep", "issn-l": "2045-2322"}, "abstract": "Cells release nano-sized membrane vesicles that are involved in intercellular communication by transferring biological information between cells. It is generally accepted that cells release at least three types of extracellular vesicles (EVs): apoptotic bodies, microvesicles and exosomes. While a wide range of putative biological functions have been attributed to exosomes, they are assumed to represent a homogenous population of EVs. We hypothesized the existence of subpopulations of exosomes with defined molecular compositions and biological properties. Density gradient centrifugation of isolated exosomes revealed the presence of two distinct subpopulations, differing in biophysical properties and their proteomic and RNA repertoires. Interestingly, the subpopulations mediated differential effects on the gene expression programmes in recipient cells. In conclusion, we demonstrate that cells release distinct exosome subpopulations with unique compositions that elicit differential effects on recipient cells. Further dissection of exosome heterogeneity will advance our understanding of exosomal biology in health and disease and accelerate the development of exosome-based diagnostics and therapeutics.", "doi": "10.1038/srep22519", "pmid": "26931825", "labels": {"Clinical Proteomics Mass spectrometry": "Technology development"}, "xrefs": [{"db": "pii", "key": "srep22519"}, {"db": "pmc", "key": "PMC4773763"}], "notes": [], "created": "2017-05-03T13:02:32.859Z", "modified": "2021-07-08T11:36:15.276Z"}, {"entity": "publication", "iuid": "150901597106460ca19322b5e9e8a83d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/150901597106460ca19322b5e9e8a83d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/150901597106460ca19322b5e9e8a83d"}}, "title": "Comprehensive Proteomic Analysis of Mesenchymal Stem Cell Exosomes Reveals Modulation of Angiogenesis via Nuclear Factor-KappaB Signaling.", "authors": [{"family": "Anderson", "given": "Johnathon D", "initials": "JD"}, {"family": "Johansson", "given": "Henrik J", "initials": "HJ"}, {"family": "Graham", "given": "Calvin S", "initials": "CS"}, {"family": "Vesterlund", "given": "Mattias", "initials": "M"}, {"family": "Pham", "given": "Missy T", "initials": "MT"}, {"family": "Bramlett", "given": "Charles S", "initials": "CS"}, {"family": "Montgomery", "given": "Elizabeth N", "initials": "EN"}, {"family": "Mellema", "given": "Matt S", "initials": "MS"}, {"family": "Bardini", "given": "Renee L", "initials": "RL"}, {"family": "Contreras", "given": "Zelenia", "initials": "Z"}, {"family": "Hoon", "given": "Madeline", "initials": "M"}, {"family": "Bauer", "given": "Gerhard", "initials": "G"}, {"family": "Fink", "given": "Kyle D", "initials": "KD"}, {"family": "Fury", "given": "Brian", "initials": "B"}, {"family": "Hendrix", "given": "Kyle J", "initials": "KJ"}, {"family": "Chedin", "given": "Frederic", "initials": "F"}, {"family": "El-Andaloussi", "given": "Samir", "initials": "S"}, {"family": "Hwang", "given": "Billie", "initials": "B"}, {"family": "Mulligan", "given": "Michael S", "initials": "MS"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Nolta", "given": "Jan A", "initials": "JA"}], "type": "journal article", "published": "2016-03-00", "journal": {"volume": "34", "issn": "1549-4918", "issue": "3", "pages": "601-613", "title": "Stem Cells", "issn-l": "1066-5099"}, "abstract": "Mesenchymal stem cells (MSC) are known to facilitate healing of ischemic tissue related diseases through proangiogenic secretory proteins. Recent studies further show that MSC derived exosomes function as paracrine effectors of angiogenesis, however, the identity of which components of the exosome proteome responsible for this effect remains elusive. To address this we used high-resolution isoelectric focusing coupled liquid chromatography tandem mass spectrometry, an unbiased high throughput proteomics approach to comprehensively characterize the proteinaceous contents of MSCs and MSC derived exosomes. We probed the proteome of MSCs and MSC derived exosomes from cells cultured under expansion conditions and under ischemic tissue simulated conditions to elucidate key angiogenic paracrine effectors present and potentially differentially expressed in these conditions. In total, 6,342 proteins were identified in MSCs and 1,927 proteins in MSC derived exosomes, representing to our knowledge the first time these proteomes have been probed comprehensively. Multilayered analyses identified several putative paracrine effectors of angiogenesis present in MSC exosomes and increased in expression in MSCs exposed to ischemic tissue-simulated conditions; these include platelet derived growth factor, epidermal growth factor, fibroblast growth factor, and most notably nuclear factor-kappaB (NFkB) signaling pathway proteins. NFkB signaling was identified as a key mediator of MSC exosome induced angiogenesis in endothelial cells by functional in vitro validation using a specific inhibitor. Collectively, the results of our proteomic analysis show that MSC derived exosomes contain a robust profile of angiogenic paracrine effectors, which have potential for the treatment of ischemic tissue-related diseases.", "doi": "10.1002/stem.2298", "pmid": "26782178", "labels": {"Clinical Proteomics Mass spectrometry": "Collaborative", "Global Proteomics and Proteogenomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC5785927"}, {"db": "mid", "key": "NIHMS932042"}], "notes": [], "created": "2017-05-03T13:02:32.246Z", "modified": "2021-07-08T11:36:15.138Z"}, {"entity": "publication", "iuid": "047859d1700e499aac6f1ba119dde6e2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/047859d1700e499aac6f1ba119dde6e2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/047859d1700e499aac6f1ba119dde6e2"}}, "title": "Multi-level omics analysis in a murine model of dystrophin loss and therapeutic restoration.", "authors": [{"family": "Roberts", "given": "Thomas C", "initials": "TC"}, {"family": "Johansson", "given": "Henrik J", "initials": "HJ"}, {"family": "McClorey", "given": "Graham", "initials": "G"}, {"family": "Godfrey", "given": "Caroline", "initials": "C"}, {"family": "Blomberg", "given": "K Emelie M", "initials": "KE"}, {"family": "Coursindel", "given": "Thibault", "initials": "T"}, {"family": "Gait", "given": "Michael J", "initials": "MJ"}, {"family": "Smith", "given": "C I Edvard", "initials": "CI"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "El Andaloussi", "given": "Samir", "initials": "S"}, {"family": "Wood", "given": "Matthew J A", "initials": "MJ"}], "type": "journal article", "published": "2015-12-01", "journal": {"volume": "24", "issn": "1460-2083", "issue": "23", "pages": "6756-6768", "title": "Hum. Mol. Genet.", "issn-l": "0964-6906"}, "abstract": "Duchenne muscular dystrophy (DMD) is a classical monogenic disorder, a model disease for genomic studies and a priority candidate for regenerative medicine and gene therapy. Although the genetic cause of DMD is well known, the molecular pathogenesis of disease and the response to therapy are incompletely understood. Here, we describe analyses of protein, mRNA and microRNA expression in the tibialis anterior of the mdx mouse model of DMD. Notably, 3272 proteins were quantifiable and 525 identified as differentially expressed in mdx muscle (P < 0.01). Therapeutic restoration of dystrophin by exon skipping induced widespread shifts in protein and mRNA expression towards wild-type expression levels, whereas the miRNome was largely unaffected. Comparison analyses between datasets showed that protein and mRNA ratios were only weakly correlated (r = 0.405), and identified a multitude of differentially affected cellular pathways, upstream regulators and predicted miRNA-target interactions. This study provides fundamental new insights into gene expression and regulation in dystrophic muscle.", "doi": "10.1093/hmg/ddv381", "pmid": "26385637", "labels": {"Bioinformatics and Expression Analysis (BEA)": null}, "xrefs": [{"db": "pii", "key": "ddv381"}, {"db": "pmc", "key": "PMC4634378"}], "notes": [], "created": "2017-05-02T12:58:24.717Z", "modified": "2021-07-08T11:36:15.131Z"}, {"entity": "publication", "iuid": "a70aaaa7899f4e879e6ae51fb735c04a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a70aaaa7899f4e879e6ae51fb735c04a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a70aaaa7899f4e879e6ae51fb735c04a"}}, "title": "Identifying and Assessing Interesting Subgroups in a Heterogeneous Population.", "authors": [{"family": "Lee", "given": "Woojoo", "initials": "W"}, {"family": "Alexeyenko", "given": "Andrey", "initials": "A"}, {"family": "Pernemalm", "given": "Maria", "initials": "M", "orcid": "0000-0003-4624-031X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f15f303cb2044cfa81719700137e3603.json"}}, {"family": "Guegan", "given": "Justine", "initials": "J"}, {"family": "Dessen", "given": "Philippe", "initials": "P"}, {"family": "Lazar", "given": "Vladimir", "initials": "V"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Pawitan", "given": "Yudi", "initials": "Y"}], "type": "journal article", "published": "2015-08-03", "journal": {"volume": "2015", "issn": "2314-6141", "issue": null, "pages": "462549", "title": "Biomed Res Int", "issn-l": "2314-6133"}, "abstract": "Biological heterogeneity is common in many diseases and it is often the reason for therapeutic failures. Thus, there is great interest in classifying a disease into subtypes that have clinical significance in terms of prognosis or therapy response. One of the most popular methods to uncover unrecognized subtypes is cluster analysis. However, classical clustering methods such as k-means clustering or hierarchical clustering are not guaranteed to produce clinically interesting subtypes. This could be because the main statistical variability--the basis of cluster generation--is dominated by genes not associated with the clinical phenotype of interest. Furthermore, a strong prognostic factor might be relevant for a certain subgroup but not for the whole population; thus an analysis of the whole sample may not reveal this prognostic factor. To address these problems we investigate methods to identify and assess clinically interesting subgroups in a heterogeneous population. The identification step uses a clustering algorithm and to assess significance we use a false discovery rate- (FDR-) based measure. Under the heterogeneity condition the standard FDR estimate is shown to overestimate the true FDR value, but this is remedied by an improved FDR estimation procedure. As illustrations, two real data examples from gene expression studies of lung cancer are provided.", "doi": "10.1155/2015/462549", "pmid": "26339613", "labels": {"Bioinformatics Support, Infrastructure and Training": null, "Bioinformatics Support and Infrastructure": null, "Bioinformatics (NBIS)": null}, "xrefs": [{"db": "pmc", "key": "PMC4539210"}], "notes": [], "created": "2017-05-02T12:57:46.628Z", "modified": "2021-07-08T11:36:54.648Z"}, {"entity": "publication", "iuid": "c2a7d6add2784a56baf3f80c90b065eb", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c2a7d6add2784a56baf3f80c90b065eb.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c2a7d6add2784a56baf3f80c90b065eb"}}, "title": "Multi-omic data analysis using Galaxy.", "authors": [{"family": "Boekel", "given": "Jorrit", "initials": "J"}, {"family": "Chilton", "given": "John M", "initials": "JM"}, {"family": "Cooke", "given": "Ira R", "initials": "IR"}, {"family": "Horvatovich", "given": "Peter L", "initials": "PL"}, {"family": "Jagtap", "given": "Pratik D", "initials": "PD"}, {"family": "K\u00e4ll", "given": "Lukas", "initials": "L"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Lukasse", "given": "Pieter", "initials": "P"}, {"family": "Moerland", "given": "Perry D", "initials": "PD"}, {"family": "Griffin", "given": "Timothy J", "initials": "TJ"}], "type": "journal article", "published": "2015-02-00", "journal": {"volume": "33", "issn": "1546-1696", "issue": "2", "pages": "137-139", "title": "Nat. Biotechnol.", "issn-l": "1087-0156"}, "abstract": null, "doi": "10.1038/nbt.3134", "pmid": "25658277", "labels": {"Clinical Proteomics Mass spectrometry": null, "Bioinformatics Support, Infrastructure and Training": null, "Bioinformatics Support and Infrastructure": null, "Bioinformatics (NBIS)": null}, "xrefs": [{"db": "pii", "key": "nbt.3134"}], "notes": [], "created": "2017-05-02T12:56:37.598Z", "modified": "2021-07-08T11:36:15.267Z"}, {"entity": "publication", "iuid": "3653dadad4754b7a8e2865919a0685d7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3653dadad4754b7a8e2865919a0685d7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3653dadad4754b7a8e2865919a0685d7"}}, "title": "Immunoproteomics using polyclonal antibodies and stable isotope-labeled affinity-purified recombinant proteins.", "authors": [{"family": "Edfors", "given": "Fredrik", "initials": "F"}, {"family": "Bostr\u00f6m", "given": "Tove", "initials": "T"}, {"family": "Forsstr\u00f6m", "given": "Bj\u00f6rn", "initials": "B"}, {"family": "Zeiler", "given": "Marlis", "initials": "M"}, {"family": "Johansson", "given": "Henrik", "initials": "H"}, {"family": "Lundberg", "given": "Emma", "initials": "E", "orcid": "0000-0001-7034-0850", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ffe6259ceb540f385861b5ae52b3055.json"}}, {"family": "Hober", "given": "Sophia", "initials": "S"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Mann", "given": "Matthias", "initials": "M"}, {"family": "Uhlen", "given": "Mathias", "initials": "M", "orcid": "0000-0002-4858-8056", "researcher": {"href": "https://publications.scilifelab.se/researcher/ff81da3cb0cf4262873b993a1b06798c.json"}}], "type": "journal article", "published": "2014-06-00", "journal": {"volume": "13", "issn": "1535-9484", "issue": "6", "pages": "1611-1624", "title": "Mol. Cell Proteomics", "issn-l": "1535-9476"}, "abstract": "The combination of immuno-based methods and mass spectrometry detection has great potential in the field of quantitative proteomics. Here, we describe a new method (immuno-SILAC) for the absolute quantification of proteins in complex samples based on polyclonal antibodies and stable isotope-labeled recombinant protein fragments to allow affinity enrichment prior to mass spectrometry analysis and accurate quantification. We took advantage of the antibody resources publicly available from the Human Protein Atlas project covering more than 80% of all human protein-coding genes. Epitope mapping revealed that a majority of the polyclonal antibodies recognized multiple linear epitopes, and based on these results, a semi-automated method was developed for peptide enrichment using polyclonal antibodies immobilized on protein A-coated magnetic beads. A protocol based on the simultaneous multiplex capture of more than 40 protein targets showed that approximately half of the antibodies enriched at least one functional peptide detected in the subsequent mass spectrometry analysis. The approach was further developed to also generate quantitative data via the addition of heavy isotope-labeled recombinant protein fragment standards prior to trypsin digestion. Here, we show that we were able to use small amounts of antibodies (50 ng per target) in this manner for efficient multiplex analysis of quantitative levels of proteins in a human HeLa cell lysate. The results suggest that polyclonal antibodies generated via immunization of recombinant protein fragments could be used for the enrichment of target peptides to allow for rapid mass spectrometry analysis taking advantage of a substantial reduction in sample complexity. The possibility of building up a proteome-wide resource for immuno-SILAC assays based on publicly available antibody resources is discussed.", "doi": "10.1074/mcp.M113.034140", "pmid": "24722731", "labels": {"Spatial Proteomics": null}, "xrefs": [{"db": "pii", "key": "M113.034140"}, {"db": "pmc", "key": "PMC4047479"}], "notes": [], "created": "2017-05-04T14:55:17.123Z", "modified": "2021-07-08T13:44:33.140Z"}, {"entity": "publication", "iuid": "42b66ac690ee431fbf466d0f44c8ccea", "links": {"self": {"href": "https://publications.scilifelab.se/publication/42b66ac690ee431fbf466d0f44c8ccea.json"}, "display": {"href": "https://publications.scilifelab.se/publication/42b66ac690ee431fbf466d0f44c8ccea"}}, "title": "SpliceVista, a tool for splice variant identification and visualization in shotgun proteomics data.", "authors": [{"family": "Zhu", "given": "Yafeng", "initials": "Y"}, {"family": "Hultin-Rosenberg", "given": "Lina", "initials": "L"}, {"family": "Forshed", "given": "Jenny", "initials": "J"}, {"family": "Branca", "given": "Rui M M", "initials": "RM"}, {"family": "Orre", "given": "Lukas M", "initials": "LM"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}], "type": "journal article", "published": "2014-06-00", "journal": {"volume": "13", "issn": "1535-9484", "issue": "6", "pages": "1552-1562", "title": "Mol. Cell Proteomics", "issn-l": "1535-9476"}, "abstract": "Alternative splicing is a pervasive process in eukaryotic organisms. More than 90% of human genes have alternatively spliced products, and aberrant splicing has been shown to be associated with many diseases. Current methods employed in the detection of splice variants include prediction by clustering of expressed sequence tags, exon microarray, and mRNA sequencing, all methods focusing on RNA-level information. There is a lack of tools for analyzing splice variants at the protein level. Here, we present SpliceVista, a tool for splice variant identification and visualization based on mass spectrometry proteomics data. SpliceVista retrieves gene structure and translated sequences from alternative splicing databases and maps MS-identified peptides to splice variants. The visualization module plots the exon composition of each splice variant and aligns identified peptides with transcript positions. If quantitative mass spectrometry data are used, SpliceVista plots the quantitative patterns for each peptide and provides users with the option to cluster peptides based on their quantitative patterns. SpliceVista can identify splice-variant-specific peptides, providing the possibility for variant-specific analysis. The tool was tested on two experimental datasets (PXD000065 and PXD000134). In A431 cells treated with gefitinib, 2983 splice-variant-specific peptides corresponding to 939 splice variants were identified. Through comparison of splice-variant-centric, protein-centric, and gene-centric quantification, several genes (e.g. EIF4H) were found to have differentially regulated splice variants after gefitinib treatment. The same discrepancy between protein-centric and splice-centric quantification was detected in the other dataset, in which induced pluripotent stem cells were compared with parental fibroblast and human embryotic stem cells. In addition, SpliceVista can be used to visualize novel splice variants inferred from peptide-level evidence. In summary, SpliceVista enables visualization, detection, and differential quantification of protein splice variants that are often missed in current proteomics pipelines.", "doi": "10.1074/mcp.M113.031203", "pmid": "24692640", "labels": {"National Genomics Infrastructure": null, "NGI Stockholm (Genomics Applications)": null, "NGI Stockholm (Genomics Production)": null}, "xrefs": [{"db": "pii", "key": "S1535-9476(20)33085-1"}, {"db": "pmc", "key": "PMC4047474"}], "notes": [], "created": "2017-05-04T14:58:44.841Z", "modified": "2021-07-08T11:36:15.190Z"}, {"entity": "publication", "iuid": "f5ae0bcb00e84e21ab0bdf4d81044a0c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f5ae0bcb00e84e21ab0bdf4d81044a0c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f5ae0bcb00e84e21ab0bdf4d81044a0c"}}, "title": "HiRIEF LC-MS enables deep proteome coverage and unbiased proteogenomics.", "authors": [{"family": "Branca", "given": "Rui M M", "initials": "RM", "orcid": "0000-0003-3890-6476", "researcher": {"href": "https://publications.scilifelab.se/researcher/87d6256540174d3da581d4572f9d182a.json"}}, {"family": "Orre", "given": "Lukas M", "initials": "LM", "orcid": "0000-0002-0384-1003", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b4e49a93b0143db88059c4d1e9fdc59.json"}}, {"family": "Johansson", "given": "Henrik J", "initials": "HJ", "orcid": "0000-0003-4729-4205", "researcher": {"href": "https://publications.scilifelab.se/researcher/18aebf211fa640f48a7c8d860c168e5a.json"}}, {"family": "Granholm", "given": "Viktor", "initials": "V"}, {"family": "Huss", "given": "Mikael", "initials": "M"}, {"family": "P\u00e9rez-Bercoff", "given": "\u00c5sa", "initials": "\u00c5"}, {"family": "Forshed", "given": "Jenny", "initials": "J"}, {"family": "K\u00e4ll", "given": "Lukas", "initials": "L", "orcid": "0000-0001-5689-9797", "researcher": {"href": "https://publications.scilifelab.se/researcher/9c9f4444f83e43d79c4772a430ca3969.json"}}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}], "type": "journal article", "published": "2014-01-00", "journal": {"title": "Nat. Methods", "issn": "1548-7105", "volume": "11", "issue": "1", "pages": "59-62", "issn-l": "1548-7091"}, "abstract": "We present a liquid chromatography-mass spectrometry (LC-MS)-based method permitting unbiased (gene prediction-independent) genome-wide discovery of protein-coding loci in higher eukaryotes. Using high-resolution isoelectric focusing (HiRIEF) at the peptide level in the 3.7-5.0 pH range and accurate peptide isoelectric point (pI) prediction, we probed the six-reading-frame translation of the human and mouse genomes and identified 98 and 52 previously undiscovered protein-coding loci, respectively. The method also enabled deep proteome coverage, identifying 13,078 human and 10,637 mouse proteins.", "doi": "10.1038/nmeth.2732", "pmid": "24240322", "labels": {"National Genomics Infrastructure": "Service", "Bioinformatics Support, Infrastructure and Training": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support and Infrastructure": "Service", "Bioinformatics (NBIS)": "Service"}, "xrefs": [{"db": "pii", "key": "nmeth.2732"}], "notes": [], "created": "2023-06-16T12:47:04.864Z", "modified": "2023-06-16T12:47:27.234Z"}, {"entity": "publication", "iuid": "5777fcc31a434305bb0a6ce50470d2fa", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5777fcc31a434305bb0a6ce50470d2fa.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5777fcc31a434305bb0a6ce50470d2fa"}}, "title": "Integrated molecular portrait of non-small cell lung cancers.", "authors": [{"family": "Lazar", "given": "Vladimir", "initials": "V"}, {"family": "Suo", "given": "Chen", "initials": "C"}, {"family": "Orear", "given": "Cedric", "initials": "C"}, {"family": "van den Oord", "given": "Joost", "initials": "J"}, {"family": "Balogh", "given": "Zsofia", "initials": "Z"}, {"family": "Guegan", "given": "Justine", "initials": "J"}, {"family": "Job", "given": "Bastien", "initials": "B"}, {"family": "Meurice", "given": "Guillaume", "initials": "G"}, {"family": "Ripoche", "given": "Hugues", "initials": "H"}, {"family": "Calza", "given": "Stefano", "initials": "S"}, {"family": "Hasmats", "given": "Johanna", "initials": "J"}, {"family": "Lundeberg", "given": "Joakim", "initials": "J", "orcid": "0000-0003-4313-1601", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a4e6ca0f29b4ead8569e2729481c3e0.json"}}, {"family": "Lacroix", "given": "Ludovic", "initials": "L"}, {"family": "Vielh", "given": "Philippe", "initials": "P"}, {"family": "Dufour", "given": "Fabienne", "initials": "F"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Napieralski", "given": "Rudolf", "initials": "R"}, {"family": "Eggermont", "given": "Alexander", "initials": "A"}, {"family": "Schmitt", "given": "Manfred", "initials": "M"}, {"family": "Cadranel", "given": "Jacques", "initials": "J"}, {"family": "Besse", "given": "Benjamin", "initials": "B"}, {"family": "Girard", "given": "Philippe", "initials": "P"}, {"family": "Blackhall", "given": "Fiona", "initials": "F"}, {"family": "Validire", "given": "Pierre", "initials": "P"}, {"family": "Soria", "given": "Jean-Charles", "initials": "JC"}, {"family": "Dessen", "given": "Philippe", "initials": "P"}, {"family": "Hansson", "given": "Johan", "initials": "J"}, {"family": "Pawitan", "given": "Yudi", "initials": "Y"}], "type": "journal article", "published": "2013-12-03", "journal": {"volume": "6", "issn": "1755-8794", "issue": null, "pages": "53", "title": "BMC Med Genomics", "issn-l": "1755-8794"}, "abstract": "Non-small cell lung cancer (NSCLC), a leading cause of cancer deaths, represents a heterogeneous group of neoplasms, mostly comprising squamous cell carcinoma (SCC), adenocarcinoma (AC) and large-cell carcinoma (LCC). The objectives of this study were to utilize integrated genomic data including copy-number alteration, mRNA, microRNA expression and candidate-gene full sequencing data to characterize the molecular distinctions between AC and SCC.\n\nComparative genomic hybridization followed by mutational analysis, gene expression and miRNA microarray profiling were performed on 123 paired tumor and non-tumor tissue samples from patients with NSCLC.\n\nAt DNA, mRNA and miRNA levels we could identify molecular markers that discriminated significantly between the various histopathological entities of NSCLC. We identified 34 genomic clusters using aCGH data; several genes exhibited a different profile of aberrations between AC and SCC, including PIK3CA, SOX2, THPO, TP63, PDGFB genes. Gene expression profiling analysis identified SPP1, CTHRC1 and GREM1 as potential biomarkers for early diagnosis of the cancer, and SPINK1 and BMP7 to distinguish between AC and SCC in small biopsies or in blood samples. Using integrated genomics approach we found in recurrently altered regions a list of three potential driver genes, MRPS22, NDRG1 and RNF7, which were consistently over-expressed in amplified regions, had wide-spread correlation with an average of ~800 genes throughout the genome and highly associated with histological types. Using a network enrichment analysis, the targets of these potential drivers were seen to be involved in DNA replication, cell cycle, mismatch repair, p53 signalling pathway and other lung cancer related signalling pathways, and many immunological pathways. Furthermore, we also identified one potential driver miRNA hsa-miR-944.\n\nIntegrated molecular characterization of AC and SCC helped identify clinically relevant markers and potential drivers, which are recurrent and stable changes at DNA level that have functional implications at RNA level and have strong association with histological subtypes.", "doi": "10.1186/1755-8794-6-53", "pmid": "24299561", "labels": {"National Genomics Infrastructure": null, "NGI Stockholm (Genomics Applications)": null, "NGI Stockholm (Genomics Production)": null}, "xrefs": [{"db": "pii", "key": "1755-8794-6-53"}, {"db": "pmc", "key": "PMC4222074"}], "notes": [], "created": "2017-05-04T14:57:50.305Z", "modified": "2021-07-08T13:26:08.184Z"}, {"entity": "publication", "iuid": "87e3d2bb0d5442fe9c4911cc26f86f2f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/87e3d2bb0d5442fe9c4911cc26f86f2f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/87e3d2bb0d5442fe9c4911cc26f86f2f"}}, "title": "Selectivity analysis of single binder assays used in plasma protein profiling.", "authors": [{"family": "Neiman", "given": "Maja", "initials": "M"}, {"family": "Fredolini", "given": "Claudia", "initials": "C", "orcid": "0000-0002-7674-2014", "researcher": {"href": "https://publications.scilifelab.se/researcher/40ac3a5823cb4f998cc8bdb96dcbf195.json"}}, {"family": "Johansson", "given": "Henrik", "initials": "H"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Nygren", "given": "Per-\u00c5ke", "initials": "P"}, {"family": "Uhl\u00e9n", "given": "Mathias", "initials": "M", "orcid": "0000-0002-4858-8056", "researcher": {"href": "https://publications.scilifelab.se/researcher/ff81da3cb0cf4262873b993a1b06798c.json"}}, {"family": "Nilsson", "given": "Peter", "initials": "P", "orcid": "0000-0002-4657-8532", "researcher": {"href": "https://publications.scilifelab.se/researcher/799bcf1cf8cf451296f4535dd4ca9dc0.json"}}, {"family": "Schwenk", "given": "Jochen M", "initials": "JM", "orcid": "0000-0001-8141-8449", "researcher": {"href": "https://publications.scilifelab.se/researcher/aba5822711b246b397fffacb7ae403b3.json"}}], "type": "journal article", "published": "2013-12-00", "journal": {"volume": "13", "issn": "1615-9861", "issue": "23-24", "pages": "3406-3410", "title": "Proteomics", "issn-l": "1615-9853"}, "abstract": "The increasing availability of antibodies toward human proteins enables broad explorations of the proteomic landscape in cells, tissues, and body fluids. This includes assays with antibody suspension bead arrays that generate protein profiles of plasma samples by flow cytometer analysis. However, antibody selectivity is context dependent so it is necessary to corroborate on-target detection over off-target binding. To address this, we describe a concept to directly verify interactions from antibody-coupled beads by analysis of their eluates by Western blots and MS. We demonstrate selective antibody binding in complex samples with antibodies toward a set of chosen proteins with different abundance in plasma and serum, and illustrate the need to adjust sample and bead concentrations accordingly. The presented approach will serve as an important tool for resolving differential protein profiles from antibody arrays within plasma biomarker discoveries.", "doi": "10.1002/pmic.201300030", "pmid": "24151238", "labels": {"Affinity Proteomics Stockholm": "Technology development"}, "xrefs": [{"db": "pmc", "key": "PMC4265267"}], "notes": [], "created": "2017-05-04T14:55:38.987Z", "modified": "2021-07-08T13:44:33.385Z"}, {"entity": "publication", "iuid": "64b1a650dbca4d7fae474646e27d6298", "links": {"self": {"href": "https://publications.scilifelab.se/publication/64b1a650dbca4d7fae474646e27d6298.json"}, "display": {"href": "https://publications.scilifelab.se/publication/64b1a650dbca4d7fae474646e27d6298"}}, "title": "Retinoic acid receptor alpha is associated with tamoxifen resistance in breast cancer.", "authors": [{"family": "Johansson", "given": "Henrik J", "initials": "HJ"}, {"family": "Sanchez", "given": "Betzabe C", "initials": "BC"}, {"family": "Mundt", "given": "Filip", "initials": "F"}, {"family": "Forshed", "given": "Jenny", "initials": "J"}, {"family": "Kovacs", "given": "Aniko", "initials": "A"}, {"family": "Panizza", "given": "Elena", "initials": "E"}, {"family": "Hultin-Rosenberg", "given": "Lina", "initials": "L"}, {"family": "Lundgren", "given": "Bo", "initials": "B"}, {"family": "Martens", "given": "Ulf", "initials": "U"}, {"family": "M\u00e1th\u00e9", "given": "Gy\u00f6ngyv\u00e9r", "initials": "G"}, {"family": "Yakhini", "given": "Zohar", "initials": "Z"}, {"family": "Helou", "given": "Khalil", "initials": "K"}, {"family": "Krawiec", "given": "Kamilla", "initials": "K"}, {"family": "Kanter", "given": "Lena", "initials": "L"}, {"family": "Hjerpe", "given": "Anders", "initials": "A"}, {"family": "St\u00e5l", "given": "Olle", "initials": "O"}, {"family": "Linderholm", "given": "Barbro K", "initials": "BK"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}], "type": "journal article", "published": "2013-07-23", "journal": {"volume": "4", "issn": "2041-1723", "issue": null, "pages": "2175", "title": "Nat Commun", "issn-l": "2041-1723"}, "abstract": "About one-third of oestrogen receptor alpha-positive breast cancer patients treated with tamoxifen relapse. Here we identify the nuclear receptor retinoic acid receptor alpha as a marker of tamoxifen resistance. Using quantitative mass spectrometry-based proteomics, we show that retinoic acid receptor alpha protein networks and levels differ in a tamoxifen-sensitive (MCF7) and a tamoxifen-resistant (LCC2) cell line. High intratumoural retinoic acid receptor alpha protein levels also correlate with reduced relapse-free survival in oestrogen receptor alpha-positive breast cancer patients treated with adjuvant tamoxifen solely. A similar retinoic acid receptor alpha expression pattern is seen in a comparable independent patient cohort. An oestrogen receptor alpha and retinoic acid receptor alpha ligand screening reveals that tamoxifen-resistant LCC2 cells have increased sensitivity to retinoic acid receptor alpha ligands and are less sensitive to oestrogen receptor alpha ligands compared with MCF7 cells. Our data indicate that retinoic acid receptor alpha may be a novel therapeutic target and a predictive factor for oestrogen receptor alpha-positive breast cancer patients treated with adjuvant tamoxifen.", "doi": "10.1038/ncomms3175", "pmid": "23868472", "labels": {"Drug Discovery and Development": "Collaborative"}, "xrefs": [{"db": "pii", "key": "ncomms3175"}, {"db": "pmc", "key": "PMC3759040"}], "notes": "Biochemical and Cellular Screening", "created": "2017-05-04T14:57:01.894Z", "modified": "2025-10-17T13:05:09.700Z"}, {"entity": "publication", "iuid": "d8f759d520a4451786bdaf27f5d04886", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d8f759d520a4451786bdaf27f5d04886.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d8f759d520a4451786bdaf27f5d04886"}}, "title": "Genomic insights into the atopic eczema-associated skin commensal yeast Malassezia sympodialis.", "authors": [{"family": "Gioti", "given": "Anastasia", "initials": "A"}, {"family": "Nystedt", "given": "Bj\u00f6rn", "initials": "B", "orcid": "0000-0001-7809-7664", "researcher": {"href": "https://publications.scilifelab.se/researcher/f0af5a168baa4b00a6fab8d3447ebfb4.json"}}, {"family": "Li", "given": "Wenjun", "initials": "W"}, {"family": "Xu", "given": "Jun", "initials": "J"}, {"family": "Andersson", "given": "Anna", "initials": "A"}, {"family": "Averette", "given": "Anna F", "initials": "AF"}, {"family": "M\u00fcnch", "given": "Karin", "initials": "K"}, {"family": "Wang", "given": "Xuying", "initials": "X"}, {"family": "Kappauf", "given": "Catharine", "initials": "C"}, {"family": "Kingsbury", "given": "Joanne M", "initials": "JM"}, {"family": "Kraak", "given": "Bart", "initials": "B"}, {"family": "Walker", "given": "Louise A", "initials": "LA"}, {"family": "Johansson", "given": "Henrik J", "initials": "HJ"}, {"family": "Holm", "given": "Tina", "initials": "T"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Stajich", "given": "Jason E", "initials": "JE"}, {"family": "Mieczkowski", "given": "Piotr", "initials": "P"}, {"family": "Kahmann", "given": "Regine", "initials": "R"}, {"family": "Kennell", "given": "John C", "initials": "JC"}, {"family": "Cardenas", "given": "Maria E", "initials": "ME"}, {"family": "Lundeberg", "given": "Joakim", "initials": "J", "orcid": "0000-0003-4313-1601", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a4e6ca0f29b4ead8569e2729481c3e0.json"}}, {"family": "Saunders", "given": "Charles W", "initials": "CW"}, {"family": "Boekhout", "given": "Teun", "initials": "T"}, {"family": "Dawson", "given": "Thomas L", "initials": "TL"}, {"family": "Munro", "given": "Carol A", "initials": "CA"}, {"family": "de Groot", "given": "Piet W J", "initials": "PW"}, {"family": "Butler", "given": "Geraldine", "initials": "G"}, {"family": "Heitman", "given": "Joseph", "initials": "J"}, {"family": "Scheynius", "given": "Annika", "initials": "A"}], "type": "comparative study", "published": "2013-01-22", "journal": {"volume": "4", "issn": "2150-7511", "issue": "1", "pages": "e00572-e00512", "title": "MBio", "issn-l": null}, "abstract": "Malassezia commensal yeasts are associated with a number of skin disorders, such as atopic eczema/dermatitis and dandruff, and they also can cause systemic infections. Here we describe the 7.67-Mbp genome of Malassezia sympodialis, a species associated with atopic eczema, and contrast its genome repertoire with that of Malassezia globosa, associated with dandruff, as well as those of other closely related fungi. Ninety percent of the predicted M. sympodialis protein coding genes were experimentally verified by mass spectrometry at the protein level. We identified a relatively limited number of genes related to lipid biosynthesis, and both species lack the fatty acid synthase gene, in line with the known requirement of these yeasts to assimilate lipids from the host. Malassezia species do not appear to have many cell wall-localized glycosylphosphatidylinositol (GPI) proteins and lack other cell wall proteins previously identified in other fungi. This is surprising given that in other fungi these proteins have been shown to mediate interactions (e.g., adhesion and biofilm formation) with the host. The genome revealed a complex evolutionary history for an allergen of unknown function, Mala s 7, shown to be encoded by a member of an amplified gene family of secreted proteins. Based on genetic and biochemical studies with the basidiomycete human fungal pathogen Cryptococcus neoformans, we characterized the allergen Mala s 6 as the cytoplasmic cyclophilin A. We further present evidence that M. sympodialis may have the capacity to undergo sexual reproduction and present a model for a pseudobipolar mating system that allows limited recombination between two linked MAT loci.\n\nMalassezia commensal yeasts are associated with a number of skin disorders. The previously published genome of M. globosa provided some of the first insights into Malassezia biology and its involvement in dandruff. Here, we present the genome of M. sympodialis, frequently isolated from patients with atopic eczema and healthy individuals. We combined comparative genomics with sequencing and functional characterization of specific genes in a population of clinical isolates and in closely related model systems. Our analyses provide insights into the evolution of allergens related to atopic eczema and the evolutionary trajectory of the machinery for sexual reproduction and meiosis. We hypothesize that M. sympodialis may undergo sexual reproduction, which has important implications for the understanding of the life cycle and virulence potential of this medically important yeast. Our findings provide a foundation for the development of genetic and genomic tools to elucidate host-microbe interactions that occur on the skin and to identify potential therapeutic targets.", "doi": "10.1128/mBio.00572-12", "pmid": "23341551", "labels": {"National Genomics Infrastructure": null, "NGI Stockholm (Genomics Applications)": null, "NGI Stockholm (Genomics Production)": null}, "xrefs": [{"db": "pii", "key": "mBio.00572-12"}, {"db": "pmc", "key": "PMC3560662"}, {"db": "GENBANK", "key": "HE999549"}, {"db": "GENBANK", "key": "HE999550"}, {"db": "GENBANK", "key": "HE999551"}, {"db": "GENBANK", "key": "HE999552"}, {"db": "GENBANK", "key": "HE999553"}, {"db": "GENBANK", "key": "HE999554"}, {"db": "GENBANK", "key": "HE999555"}, {"db": "GENBANK", "key": "HE999556"}, {"db": "GENBANK", "key": "HE999557"}, {"db": "GENBANK", "key": "HE999558"}, {"db": "GENBANK", "key": "HE999559"}, {"db": "GENBANK", "key": "HE999560"}, {"db": "GENBANK", "key": "HE999561"}, {"db": "GENBANK", "key": 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"GENBANK", "key": "JX964800"}, {"db": "GENBANK", "key": "JX964801"}, {"db": "GENBANK", "key": "JX964802"}, {"db": "GENBANK", "key": "JX964840"}, {"db": "GENBANK", "key": "JX964841"}, {"db": "GENBANK", "key": "JX964842"}, {"db": "GENBANK", "key": "JX964843"}, {"db": "GENBANK", "key": "JX964844"}, {"db": "GENBANK", "key": "JX964845"}, {"db": "GENBANK", "key": "JX964846"}, {"db": "GENBANK", "key": "JX964847"}, {"db": "GENBANK", "key": "JX964848"}, {"db": "GENBANK", "key": "JX964849"}, {"db": "GENBANK", "key": "JX964850"}], "notes": [], "created": "2017-05-04T14:58:03.302Z", "modified": "2021-07-08T13:26:08.367Z"}, {"entity": "publication", "iuid": "2e8a48c6bcb0435e81f13645120db225", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2e8a48c6bcb0435e81f13645120db225.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2e8a48c6bcb0435e81f13645120db225"}}, "title": "Proteomic screen reveals Fbw7 as a modulator of the NF-\u03baB pathway.", "authors": [{"family": "Arabi", "given": "Azadeh", "initials": "A"}, {"family": "Ullah", "given": "Karim", "initials": "K"}, {"family": "Branca", "given": "Rui M M", "initials": "RM"}, {"family": "Johansson", "given": "Johan", "initials": "J"}, {"family": "Bandarra", "given": "Daniel", "initials": "D"}, {"family": "Haneklaus", "given": "Moritz", "initials": "M"}, {"family": "Fu", "given": "Jing", "initials": "J"}, {"family": "Ari\u00ebs", "given": "Ingrid", "initials": "I"}, {"family": "Nilsson", "given": "Peter", "initials": "P", "orcid": "0000-0002-4657-8532", "researcher": {"href": "https://publications.scilifelab.se/researcher/799bcf1cf8cf451296f4535dd4ca9dc0.json"}}, {"family": "Den Boer", "given": "Monique L", "initials": "ML"}, {"family": "Pokrovskaja", "given": "Katja", "initials": "K"}, {"family": "Grand\u00e9r", "given": "Dan", "initials": "D"}, {"family": "Xiao", "given": "Gutian", "initials": "G"}, {"family": "Rocha", "given": "Sonia", "initials": "S"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Sangfelt", "given": "Olle", "initials": "O"}], "type": "journal article", "published": "2012-08-07", "journal": {"volume": "3", "issn": "2041-1723", "issue": null, "pages": "976", "title": "Nat Commun", "issn-l": "2041-1723"}, "abstract": "Fbw7 is a ubiquitin-ligase that targets several oncoproteins for proteolysis, but the full range of Fbw7 substrates is not known. Here we show that by performing quantitative proteomics combined with degron motif searches, we effectively screened for a more complete set of Fbw7 targets. We identify 89 putative Fbw7 substrates, including several disease-associated proteins. The transcription factor NF-\u03baB2 (p100/p52) is one of the candidate Fbw7 substrates. We show that Fbw7 interacts with p100 via a conserved degron and that it promotes degradation of p100 in a GSK3\u03b2 phosphorylation-dependent manner. Fbw7 inactivation increases p100 levels, which in the presence of NF-\u03baB pathway stimuli, leads to increased p52 levels and activity. Accordingly, the apoptotic threshold can be increased by loss of Fbw7 in a p100-dependent manner. In conclusion, Fbw7-mediated destruction of p100 is a regulatory component restricting the response to NF-\u03baB2 pathway stimulation.", "doi": "10.1038/ncomms1975", "pmid": "22864569", "labels": {"Bioinformatics Support, Infrastructure and Training": null, "Bioinformatics Support and Infrastructure": null, "Bioinformatics (NBIS)": ""}, "xrefs": [{"db": "pii", "key": "ncomms1975"}, {"db": "pmc", "key": "PMC4354031"}], "notes": [], "created": "2017-05-04T14:56:18.815Z", "modified": "2021-07-08T11:36:15.152Z"}]}