{"entity": "researcher", "timestamp": "2026-06-09T23:42:26.593Z", "family": "Vesterlund", "given": "Mattias", "initials": "M", "orcid": "0000-0001-9471-6592", "affiliations": [], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/0942e438993b494db2a3db914852c808.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/0942e438993b494db2a3db914852c808"}}, "publications": [{"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": "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": "e62c3fd9a0844674ac981a6802d184f3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e62c3fd9a0844674ac981a6802d184f3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e62c3fd9a0844674ac981a6802d184f3"}}, "title": "Prediction model for drug response of acute myeloid leukemia patients.", "authors": [{"family": "Trac", "given": "Quang Thinh", "initials": "QT"}, {"family": "Pawitan", "given": "Yudi", "initials": "Y"}, {"family": "Mou", "given": "Tian", "initials": "T"}, {"family": "Erkers", "given": "Tom", "initials": "T"}, {"family": "\u00d6stling", "given": "P\u00e4ivi", "initials": "P"}, {"family": "Bohlin", "given": "Anna", "initials": "A"}, {"family": "\u00d6sterroos", "given": "Albin", "initials": "A", "orcid": "0000-0001-8749-7299", "researcher": {"href": "https://publications.scilifelab.se/researcher/47a3ea9e722b4c72a7f00a61b5c9fe0a.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"}}, {"family": "Siavelis", "given": "Ioannis", "initials": "I"}, {"family": "B\u00e4ckvall", "given": "Helena", "initials": "H"}, {"family": "Kiviluoto", "given": "Santeri", "initials": "S"}, {"family": "Orre", "given": "Lukas M", "initials": "LM"}, {"family": "Rantalainen", "given": "Mattias", "initials": "M"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J"}, {"family": "Lehmann", "given": "S\u00f6ren", "initials": "S"}, {"family": "Kallioniemi", "given": "Olli", "initials": "O"}, {"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": "2023-03-24", "journal": {"title": "NPJ Precis Oncol", "issn": "2397-768X", "volume": "7", "issue": "1", "pages": "32", "issn-l": null}, "abstract": "Despite some encouraging successes, predicting the therapy response of acute myeloid leukemia (AML) patients remains highly challenging due to tumor heterogeneity. Here we aim to develop and validate MDREAM, a robust ensemble-based prediction model for drug response in AML based on an integration of omics data, including mutations and gene expression, and large-scale drug testing. Briefly, MDREAM is first trained in the BeatAML cohort (n = 278), and then validated in the BeatAML (n = 183) and two external cohorts, including a Swedish AML cohort (n = 45) and a relapsed/refractory acute leukemia cohort (n = 12). The final prediction is based on 122 ensemble models, each corresponding to a drug. A confidence score metric is used to convey the uncertainty of predictions; among predictions with a confidence score >0.75, the validated proportion of good responders is 77%. The Spearman correlations between the predicted and the observed drug response are 0.68 (95% CI: [0.64, 0.68]) in the BeatAML validation set, -0.49 (95% CI: [-0.53, -0.44]) in the Swedish cohort and 0.59 (95% CI: [0.51, 0.67]) in the relapsed/refractory cohort. A web-based implementation of MDREAM is publicly available at https://www.meb.ki.se/shiny/truvu/MDREAM/ .", "doi": "10.1038/s41698-023-00374-z", "pmid": "36964195", "labels": {"Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10039068"}, {"db": "pii", "key": "10.1038/s41698-023-00374-z"}], "notes": [], "created": "2023-11-27T21:49:49.856Z", "modified": "2024-01-16T13:48:33.829Z"}, {"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": "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": "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": "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": "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": "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"}]}