{"entity": "researcher", "timestamp": "2026-05-19T01:13:31.810Z", "family": "Micke", "given": "Patrick", "initials": "P", "orcid": "0000-0003-1210-5961", "affiliations": [], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/fc0cba74e74a4c39a8f96319cb9a3034.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/fc0cba74e74a4c39a8f96319cb9a3034"}}, "publications": [{"entity": "publication", "iuid": "823c71158dcd4b9fb085d01e55d13e48", "links": {"self": {"href": "https://publications.scilifelab.se/publication/823c71158dcd4b9fb085d01e55d13e48.json"}, "display": {"href": "https://publications.scilifelab.se/publication/823c71158dcd4b9fb085d01e55d13e48"}}, "title": "scFFPE-ATAC enables high-throughput single cell chromatin accessibility profiling in formalin-fixed paraffin-embedded samples.", "authors": [{"family": "Yadav", "given": "Ram Prakash", "initials": "RP"}, {"family": "Xing", "given": "Pengwei", "initials": "P"}, {"family": "Zhao", "given": "Miao", "initials": "M", "orcid": "0000-0002-4895-1177", "researcher": {"href": "https://publications.scilifelab.se/researcher/b9c4e2515b414dee94aaeca71569699b.json"}}, {"family": "Hollander", "given": "Peter", "initials": "P"}, {"family": "Strell", "given": "Carina", "initials": "C", "orcid": "0000-0002-3783-7256", "researcher": {"href": "https://publications.scilifelab.se/researcher/eb77b417ef2b479fb267969c3a557617.json"}}, {"family": "Xie", "given": "Minglu", "initials": "M"}, {"family": "Salehi", "given": "Maede", "initials": "M"}, {"family": "Torell", "given": "Emma", "initials": "E"}, {"family": "Sj\u00f6blom", "given": "Tobias", "initials": "T", "orcid": "0000-0001-6668-4140", "researcher": {"href": "https://publications.scilifelab.se/researcher/909f00a5bf6e465f9ff560b12bcd863a.json"}}, {"family": "Enblad", "given": "Gunilla", "initials": "G", "orcid": "0000-0002-0594-724X", "researcher": {"href": "https://publications.scilifelab.se/researcher/11313af3f4a241ecb93af23ab2652195.json"}}, {"family": "Amini", "given": "Rose-Marie", "initials": "RM", "orcid": "0000-0003-0901-5252", "researcher": {"href": "https://publications.scilifelab.se/researcher/c157abcd61fa4900b5ad502b408d6d95.json"}}, {"family": "Swartling", "given": "Fredrik Johansson", "initials": "FJ", "orcid": "0000-0002-8460-4367", "researcher": {"href": "https://publications.scilifelab.se/researcher/69679cebbc90496f9c5b32f56d966654.json"}}, {"family": "Glimelius", "given": "Ingrid", "initials": "I"}, {"family": "Micke", "given": "Patrick", "initials": "P", "orcid": "0000-0003-1210-5961", "researcher": {"href": "https://publications.scilifelab.se/researcher/fc0cba74e74a4c39a8f96319cb9a3034.json"}}, {"family": "Hellstr\u00f6m", "given": "Mats", "initials": "M"}, {"family": "Chen", "given": "Xingqi", "initials": "X", "orcid": "0000-0002-5657-2839", "researcher": {"href": "https://publications.scilifelab.se/researcher/ef7ddc09e57745909175e41ac2d1b647.json"}}], "type": "journal article", "published": "2025-11-14", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "16", "issue": "1", "pages": "10022", "issn-l": "2041-1723"}, "abstract": "Formalin-fixed paraffin-embedded (FFPE) samples are the gold standard for tissue preservation in clinical and research settings. Current single-cell chromatin accessibility technologies cannot resolve cell-type-specific epigenetic profiles in FFPE tissues due to extensive DNA damage. We present scFFPE-ATAC, a high-throughput single-cell chromatin accessibility assay for FFPE samples that integrates an FFPE-adapted Tn5 transposase, ultra-high-throughput DNA barcoding (>56 million barcodes per run), T7 promoter-mediated DNA damage repair, and in vitro transcription. We benchmark scFFPE-ATAC on FFPE mouse spleen and validate its performance against fresh tissue. We apply it to human lymph node samples archived for 8-12 years and to lung cancer FFPE tissues, revealing distinct regulatory trajectories between tumor center and invasive edge. Analysis of archived follicular lymphoma and transformed diffuse large B-cell lymphoma samples identifies relapse- and transformation-associated epigenetic dynamics. scFFPE-ATAC enables retrospective, spatial, and mechanistic epigenetic studies in long-term archived specimens.", "doi": "10.1038/s41467-025-66170-4", "pmid": "41238550", "labels": {"National Genomics Infrastructure": "Service", "NGI Short read": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-025-66170-4"}, {"db": "pmc", "key": "PMC12618699"}], "notes": [], "created": "2025-11-17T09:00:46.632Z", "modified": "2025-11-17T09:00:47.092Z"}, {"entity": "publication", "iuid": "b287cd082dda431aa1c239aa37ea3454", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b287cd082dda431aa1c239aa37ea3454.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b287cd082dda431aa1c239aa37ea3454"}}, "title": "Spatial TCR clonality and clonal expansion in the in situ microenvironment of non-small cell lung cancer.", "authors": [{"family": "Yu", "given": "Hui", "initials": "H", "orcid": "0009-0000-0563-3243", "researcher": {"href": "https://publications.scilifelab.se/researcher/accd698620e64b64949a408b5c2c6a22.json"}}, {"family": "Magoulopoulou", "given": "Anastasia", "initials": "A"}, {"family": "Amini", "given": "Rose-Marie", "initials": "RM"}, {"family": "Chatzinikolaou", "given": "Maria Paraskevi", "initials": "MP"}, {"family": "Horie", "given": "Masafumi", "initials": "M"}, {"family": "Lindberg", "given": "Amanda", "initials": "A"}, {"family": "Mezheyeuski", "given": "Artur", "initials": "A"}, {"family": "Backman", "given": "Max", "initials": "M"}, {"family": "Metousis", "given": "Andreas", "initials": "A"}, {"family": "Brunnstr\u00f6m", "given": "Hans", "initials": "H"}, {"family": "Marincevic", "given": "Millaray", "initials": "M"}, {"family": "Botling", "given": "Johan", "initials": "J"}, {"family": "Mattsson", "given": "Johanna Sofia Margareta", "initials": "JSM"}, {"family": "K\u00e4rre", "given": "Klas", "initials": "K"}, {"family": "Leandersson", "given": "Karin", "initials": "K"}, {"family": "Nilsson", "given": "Mats", "initials": "M"}, {"family": "Strell", "given": "Carina", "initials": "C"}, {"family": "Micke", "given": "Patrick", "initials": "P", "orcid": "0000-0003-1210-5961", "researcher": {"href": "https://publications.scilifelab.se/researcher/fc0cba74e74a4c39a8f96319cb9a3034.json"}}], "type": "journal article", "published": "2025-08-27", "journal": {"title": "J Immunother Cancer", "issn": "2051-1426", "volume": "13", "issue": "8", "issn-l": null}, "abstract": "T-cell activation and clonal expansion are essential to effective immunotherapy responses in non-small cell lung cancer (NSCLC). The distribution of T-cell clones may offer insights into immunogenic mechanisms and imply potential prognostic and predictive information.\n\nWe analyzed \u03b1/\u03b2 T-cell receptor (TCR) clonality using RNA-sequencing of bulk frozen tumor tissue from 182 patients with NSCLC. The data was integrated with molecular and clinical characteristics, extensive in situ imaging, and spatial sequencing of the tumor immune microenvironment. TCR clonality was also determined in an independent cohort of nine patients with immune checkpoint-treated NSCLC.\n\nTCR clonality (Gini index) patterns ranged from high T-cell clone diversity with high evenness (low Gini index) to clonal dominance with low evenness (high Gini index). Generally, TCR clonality in cancer was lower than in matched normal lung parenchyma distant from the tumor (p=0.021). The TCR clonality distribution between adenocarcinoma and squamous cell carcinoma was similar; however, smokers showed a higher Gini index. While in the operated patient with NSCLC cohort, TCR clonality was not prognostic, in an immune checkpoint inhibitor-treated cohort, high TCR clonality was associated with better therapy response (p=0.016) and prolonged survival (p=0.003, median survival 13.8 vs 2.9 months). On the genomic level, a higher Gini index correlated strongly with a lower frequency of epidermal growth factor receptor (EGFR) and adenomatous polypsis coli (APC) gene mutations, but a higher frequency of P53 mutations, and a higher tumor mutation burden. In-depth characterization of the tumor tissue revealed that high TCR clonality was associated with an activated, inflamed tumor phenotype (PRF1, GZMA, GZMB, INFG) with exhaustion signatures (LAG3, TIGIT, IDO1, PD-1, PD-L1). Correspondingly, PD-1+, CD3+, CD8A+, CD163+, and CD138+immune cells infiltrated cancer tissue with high TCR clonality. In situ sequencing recovered single dominant T-cell clones within the patient tumor tissue, which were predominantly of the CD8 subtype and localized closer to tumor cells.\n\nOur robust analysis pipeline characterized diverse TCR repertoires linked to distinct genotypes and immunologic tumor phenotypes. The spatial clustering of expanded T-cell clones and their association with immunological activation underscores a functional, clinically relevant immune response, particularly in patients with NSCLC treated with checkpoint inhibitors.", "doi": "10.1136/jitc-2025-012089", "pmid": "40866291", "labels": {"In Situ Sequencing": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC12434955"}, {"db": "pii", "key": "jitc-2025-012089"}], "notes": [], "created": "2025-11-28T06:52:14.774Z", "modified": "2025-11-28T06:52:14.874Z"}, {"entity": "publication", "iuid": "674ed939c1a74109b72a53ce6576ea0d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/674ed939c1a74109b72a53ce6576ea0d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/674ed939c1a74109b72a53ce6576ea0d"}}, "title": "Unlocking novel T cell-based immunotherapy for hepatocellular carcinoma through neoantigen-driven T cell receptor isolation.", "authors": [{"family": "Maravelia", "given": "Panagiota", "initials": "P"}, {"family": "Yao", "given": "Haidong", "initials": "H", "orcid": "0009-0007-4791-5063", "researcher": {"href": "https://publications.scilifelab.se/researcher/03a40cff36064374912d40cc5a9c65db.json"}}, {"family": "Cai", "given": "Curtis", "initials": "C", "orcid": "0000-0002-3490-4361", "researcher": {"href": "https://publications.scilifelab.se/researcher/0ea25e71e96246d89437270a12cc9e47.json"}}, {"family": "Nascimento Silva", "given": "Daniela", "initials": "D", "orcid": "0000-0003-2165-4989", "researcher": {"href": "https://publications.scilifelab.se/researcher/061bbf2c5a864c5c9e852fcab907d29e.json"}}, {"family": "Fransson", "given": "Jennifer", "initials": "J", "orcid": "0000-0003-4762-901X", "researcher": {"href": "https://publications.scilifelab.se/researcher/30428cafc89647768f6c69eecf98efcf.json"}}, {"family": "Nilsson", "given": "Ola B", "initials": "OB", "orcid": "0000-0002-7516-1760", "researcher": {"href": "https://publications.scilifelab.se/researcher/096ce3bf888b4ad395d53bb3c11f6946.json"}}, {"family": "Lu", "given": "Yong-Chen William", "initials": "YW", "orcid": "0000-0002-0275-9825", "researcher": {"href": "https://publications.scilifelab.se/researcher/fa8d7936625c42078b815953810ee136.json"}}, {"family": "Micke", "given": "Patrick", "initials": "P", "orcid": "0000-0003-1210-5961", "researcher": {"href": "https://publications.scilifelab.se/researcher/fc0cba74e74a4c39a8f96319cb9a3034.json"}}, {"family": "Botling", "given": "Johan", "initials": "J"}, {"family": "Gatto", "given": "Francesca", "initials": "F"}, {"family": "Rovesti", "given": "Giulia", "initials": "G", "orcid": "0000-0002-2761-9482", "researcher": {"href": "https://publications.scilifelab.se/researcher/cd6c4824c71c44378a7f45649766f4cd.json"}}, {"family": "Carlsten", "given": "Mattias", "initials": "M", "orcid": "0000-0001-9815-0012", "researcher": {"href": "https://publications.scilifelab.se/researcher/7dadae83c2494c7abc65118f04e1b6b6.json"}}, {"family": "Sallberg", "given": "Matti", "initials": "M", "orcid": "0000-0002-8858-5132", "researcher": {"href": "https://publications.scilifelab.se/researcher/89d4712be75441d6b49aca02c600bc70.json"}}, {"family": "St\u00e5l", "given": "Per", "initials": "P"}, {"family": "Jorns", "given": "Carl", "initials": "C", "orcid": "0000-0001-7727-8113", "researcher": {"href": "https://publications.scilifelab.se/researcher/59d387bd893f45bdb3663a0ef3aae88a.json"}}, {"family": "Buggert", "given": "Marcus", "initials": "M", "orcid": "0000-0003-0633-1719", "researcher": {"href": "https://publications.scilifelab.se/researcher/9a54e4b5136642eeafa77ac5118a0c81.json"}}, {"family": "Pasetto", "given": "Anna", "initials": "A", "orcid": "0000-0002-5254-2173", "researcher": {"href": "https://publications.scilifelab.se/researcher/781c8b467fa144e494d13c7a3e80b4fc.json"}}], "type": "journal article", "published": "2025-06-06", "journal": {"title": "Gut", "issn": "1468-3288", "volume": "74", "issue": "7", "pages": "1125-1136", "issn-l": "0017-5749"}, "abstract": "Tumour-infiltrating T cells can mediate both antitumour immunity and promote tumour progression by creating an immunosuppressive environment. This dual role is especially relevant in hepatocellular carcinoma (HCC), characterised by a unique microenvironment and limited success with current immunotherapy.\n\nWe evaluated T cell responses in patients with advanced HCC by analysing tumours, liver flushes and liver-draining lymph nodes, to understand whether reactive T cell populations could be identified despite the immunosuppressive environment.\n\nT cells isolated from clinical samples were tested for reactivity against predicted neoantigens. Single-cell RNA sequencing was employed to evaluate the transcriptomic and proteomic profiles of antigen-experienced T cells. Neoantigen-reactive T cells expressing 4-1BB were isolated and characterised through T-cell receptor (TCR)-sequencing.\n\nBioinformatic analysis identified 542 candidate neoantigens from seven patients. Of these, 78 neoantigens, along with 11 hotspot targets from HCC driver oncogenes, were selected for ex vivo T cell stimulation. Reactivity was confirmed in co-culture assays for 14 targets, with most reactive T cells derived from liver flushes and lymph nodes. Liver flush-derived T cells exhibited central memory and effector memory CD4+ with cytotoxic effector profiles. In contrast, tissue-resident memory CD4+ and CD8+ T cells with an exhausted profile were primarily identified in the draining lymph nodes.\n\nThese findings offer valuable insights into the functional profiles of neoantigen-reactive T cells within and surrounding the HCC microenvironment. T cells isolated from liver flushes and tumour-draining lymph nodes may serve as a promising source of reactive T cells and TCRs for further use in immunotherapy for HCC.", "doi": "10.1136/gutjnl-2024-334148", "pmid": "39832892", "labels": {"Bioinformatics (NBIS)": "Collaborative", "Bioinformatics Support and Infrastructure": "Collaborative", "Bioinformatics Support, Infrastructure and Training": "Collaborative", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Production)": "Service", "NGI Short read": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12611799"}, {"db": "pii", "key": "gutjnl-2024-334148"}], "notes": [], "created": "2025-11-19T08:23:34.477Z", "modified": "2025-11-21T15:22:04.326Z"}, {"entity": "publication", "iuid": "21eb44200f3c4f3fb0553c2b13a36e41", "links": {"self": {"href": "https://publications.scilifelab.se/publication/21eb44200f3c4f3fb0553c2b13a36e41.json"}, "display": {"href": "https://publications.scilifelab.se/publication/21eb44200f3c4f3fb0553c2b13a36e41"}}, "title": "Matched Analyses of Brain Metastases versus Primary Non-Small Cell Lung Cancer Reveal a Unique microRNA Signature.", "authors": [{"family": "Tsakonas", "given": "Georgios", "initials": "G", "orcid": "0000-0003-4397-7391", "researcher": {"href": "https://publications.scilifelab.se/researcher/8f935b4e6f564afdbe3c22e2a376c98d.json"}}, {"family": "Koulouris", "given": "Andreas", "initials": "A"}, {"family": "Kazmierczak", "given": "Dominika", "initials": "D"}, {"family": "Botling", "given": "Johan", "initials": "J"}, {"family": "Ortiz-Villalon", "given": "Cristian", "initials": "C"}, {"family": "Nord", "given": "Helena", "initials": "H"}, {"family": "Lindskog", "given": "Magnus", "initials": "M", "orcid": "0000-0001-9484-1983", "researcher": {"href": "https://publications.scilifelab.se/researcher/1592b4e2f1354bdd8b35f384dcac78c2.json"}}, {"family": "Sandelin", "given": "Martin", "initials": "M"}, {"family": "Micke", "given": "Patrick", "initials": "P", "orcid": "0000-0003-1210-5961", "researcher": {"href": "https://publications.scilifelab.se/researcher/fc0cba74e74a4c39a8f96319cb9a3034.json"}}, {"family": "Hydbring", "given": "Per", "initials": "P"}, {"family": "Ekman", "given": "Simon", "initials": "S", "orcid": "0000-0002-8343-6226", "researcher": {"href": "https://publications.scilifelab.se/researcher/0fcb2b2956a84f43a7b485573f445ff2.json"}}], "type": "journal article", "published": "2022-12-22", "journal": {"title": "Int J Mol Sci", "issn": "1422-0067", "volume": "24", "issue": "1", "issn-l": null}, "abstract": "Distant spreading of tumor cells to the central nervous system in non-small cell lung cancer (NSCLC) occurs frequently and poses major clinical issues due to limited treatment options. RNAs displaying differential expression in brain metastasis versus primary NSCLC may explain distant tumor growth and may potentially be used as therapeutic targets. In this study, we conducted systematic microRNA expression profiling from tissue biopsies of primary NSCLC and brain metastases from 25 patients. RNA analysis was performed using the nCounter Human v3 miRNA Expression Assay, NanoString technologies, followed by differential expression analysis and in silico target gene pathway analysis. We uncovered a panel of 11 microRNAs with differential expression and excellent diagnostic performance in brain metastasis versus primary NSCLC. Five microRNAs were upregulated in brain metastasis (miR-129-2-3p, miR-124-3p, miR-219a-2-3p, miR-219a-5p, and miR-9-5p) and six microRNAs were downregulated in brain metastasis (miR-142-3p, miR-150-5p, miR-199b-5p, miR-199a-3p, miR-199b-5p, and miR-199a-5p). The differentially expressed microRNAs were predicted to converge on distinct target gene networks originating from five to twelve core target genes. In conclusion, we uncovered a unique microRNA profile linked to two target gene networks. Our results highlight the potential of specific microRNAs as biomarkers for brain metastasis in NSCLC and indicate plausible mechanistic connections.", "doi": "10.3390/ijms24010193", "pmid": "36613642", "labels": {"Clinical Genomics Uppsala": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC9820685"}, {"db": "pii", "key": "ijms24010193"}], "notes": [], "created": "2025-02-14T13:30:14.859Z", "modified": "2025-02-14T13:30:15.384Z"}, {"entity": "publication", "iuid": "b420e68207ea460b8ba66d45e3ab9e1c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b420e68207ea460b8ba66d45e3ab9e1c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b420e68207ea460b8ba66d45e3ab9e1c"}}, "title": "Plasma Proteome Fingerprints Reveal Distinctiveness and Clinical Outcome of SARS-CoV-2 Infection", "authors": [{"family": "Bauer", "given": "Wolfgang", "initials": "W", "orcid": "0000-0002-1063-3237", "researcher": {"href": "https://publications.scilifelab.se/researcher/ec558a1b9e4141c5b41172c67430c47f.json"}}, {"family": "Weber", "given": "Marcus", "initials": "M"}, {"family": "Diehl-Wiesenecker", "given": "Eva", "initials": "E"}, {"family": "Galtung", "given": "Noa", "initials": "N", "orcid": "0000-0002-4379-9516", "researcher": {"href": "https://publications.scilifelab.se/researcher/46ba19f11dea43f48550aa84d142ca5b.json"}}, {"family": "Prpic", "given": "Monika", "initials": "M"}, {"family": "Somasundaram", "given": "Rajan", "initials": "R"}, {"family": "Tauber", "given": "Rudolf", "initials": "R"}, {"family": "Schwenk", "given": "Jochen M", "initials": "JM", "orcid": "0000-0001-8141-8449", "researcher": {"href": "https://publications.scilifelab.se/researcher/aba5822711b246b397fffacb7ae403b3.json"}}, {"family": "Micke", "given": "Patrick", "initials": "P", "orcid": "0000-0003-1210-5961", "researcher": {"href": "https://publications.scilifelab.se/researcher/fc0cba74e74a4c39a8f96319cb9a3034.json"}}, {"family": "Kappert", "given": "Kai", "initials": "K", "orcid": "0000-0001-6976-0428", "researcher": {"href": "https://publications.scilifelab.se/researcher/95a7f818f3c6463caae1e053f913dd07.json"}}], "type": "journal-article", "published": "2021-12-07", "journal": {"title": "Viruses", "issn": "1999-4915", "issn-l": "1999-4915", "volume": "13", "issue": "12", "pages": "2456"}, "abstract": null, "doi": "10.3390/v13122456", "pmid": null, "labels": {"Affinity Proteomics Stockholm": "Service"}, "xrefs": [], "notes": [], "created": "2021-12-08T07:42:07.712Z", "modified": "2023-08-02T09:58:36.077Z"}, {"entity": "publication", "iuid": "f150e8e23a9a403d8ed0d635081a5292", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f150e8e23a9a403d8ed0d635081a5292.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f150e8e23a9a403d8ed0d635081a5292"}}, "title": "An integrative proteomics method identifies a regulator of translation during stem cell maintenance and differentiation.", "authors": [{"family": "Sabatier", "given": "Pierre", "initials": "P", "orcid": "0000-0002-2734-1791", "researcher": {"href": "https://publications.scilifelab.se/researcher/1a75556311084e2b827ab1f646d7a16c.json"}}, {"family": "Beusch", "given": "Christian M", "initials": "CM", "orcid": "0000-0001-9100-8283", "researcher": {"href": "https://publications.scilifelab.se/researcher/278e50b11a3c4ef69b6e2708f99b5f3e.json"}}, {"family": "Saei", "given": "Amir A", "initials": "AA", "orcid": "0000-0002-2639-6328", "researcher": {"href": "https://publications.scilifelab.se/researcher/6f1694ffdcd94a55b6c172a854706e0f.json"}}, {"family": "Aoun", "given": "Mike", "initials": "M"}, {"family": "Moruzzi", "given": "Noah", "initials": "N"}, {"family": "Coelho", "given": "Ana", "initials": "A"}, {"family": "Leijten", "given": "Niels", "initials": "N", "orcid": "0000-0002-7305-7249", "researcher": {"href": "https://publications.scilifelab.se/researcher/52533fb586904f1598abab4fe93c8b8f.json"}}, {"family": "Nordenskj\u00f6ld", "given": "Magnus", "initials": "M"}, {"family": "Micke", "given": "Patrick", "initials": "P", "orcid": "0000-0003-1210-5961", "researcher": {"href": "https://publications.scilifelab.se/researcher/fc0cba74e74a4c39a8f96319cb9a3034.json"}}, {"family": "Maltseva", "given": "Diana", "initials": "D", "orcid": "0000-0002-4960-5348", "researcher": {"href": "https://publications.scilifelab.se/researcher/4091fbe97bf84c76b279377cb71f61e9.json"}}, {"family": "Tonevitsky", "given": "Alexander G", "initials": "AG"}, {"family": "Millischer", "given": "Vincent", "initials": "V"}, {"family": "Carlos Villaescusa", "given": "J", "initials": "J"}, {"family": "Kadekar", "given": "Sandeep", "initials": "S"}, {"family": "Gaetani", "given": "Massimiliano", "initials": "M", "orcid": "0000-0001-5610-0797", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b58e5cef5224fdcbdcd626fb798b169.json"}}, {"family": "Altynbekova", "given": "Kamilya", "initials": "K"}, {"family": "Kel", "given": "Alexander", "initials": "A"}, {"family": "Berggren", "given": "Per-Olof", "initials": "P"}, {"family": "Simonson", "given": "Oscar", "initials": "O"}, {"family": "Grinnemo", "given": "Karl-Henrik", "initials": "K"}, {"family": "Holmdahl", "given": "Rikard", "initials": "R", "orcid": "0000-0002-4969-2576", "researcher": {"href": "https://publications.scilifelab.se/researcher/49e60d22dd1a4dd1a4ca5a50d9fc4fc7.json"}}, {"family": "Rodin", "given": "Sergey", "initials": "S", "orcid": "0000-0002-6954-1986", "researcher": {"href": "https://publications.scilifelab.se/researcher/2371c1f6b98c46c495530ac860a2beb8.json"}}, {"family": "Zubarev", "given": "Roman A", "initials": "RA", "orcid": "0000-0001-9839-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/e971b9cdec2b4411934f9c5d535da8b4.json"}}], "type": "journal article", "published": "2021-11-12", "journal": {"title": "Nat Commun", "issn": "2041-1723", "issn-l": "2041-1723", "volume": "12", "issue": "1", "pages": "6558"}, "abstract": "Detailed characterization of cell type transitions is essential for cell biology in general and particularly for the development of stem cell-based therapies in regenerative medicine. To systematically study such transitions, we introduce a method that simultaneously measures protein expression and thermal stability changes in cells and provide the web-based visualization tool ProteoTracker. We apply our method to study differences between human pluripotent stem cells and several cell types including their parental cell line and differentiated progeny. We detect alterations of protein properties in numerous cellular pathways and components including ribosome biogenesis and demonstrate that modulation of ribosome maturation through SBDS protein can be helpful for manipulating cell stemness in vitro. Using our integrative proteomics approach and the web-based tool, we uncover a molecular basis for the uncoupling of robust transcription from parsimonious translation in stem cells and propose a method for maintaining pluripotency in vitro.", "doi": "10.1038/s41467-021-26879-4", "pmid": "34772928", "labels": {"Chemical Proteomics": "Technology development"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-021-26879-4"}, {"db": "pmc", "key": "PMC8590018"}], "notes": [], "created": "2021-11-29T17:23:45.777Z", "modified": "2024-01-18T23:36:09.097Z"}, {"entity": "publication", "iuid": "a10ef57139814fb299f0fd7187b6b2d3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a10ef57139814fb299f0fd7187b6b2d3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a10ef57139814fb299f0fd7187b6b2d3"}}, "title": "FGFR1 overexpression in non-small cell lung cancer is mediated by genetic and epigenetic mechanisms and is a determinant of FGFR1 inhibitor response.", "authors": [{"family": "Bogatyrova", "given": "Olga", "initials": "O"}, {"family": "Mattsson", "given": "Johanna S M", "initials": "JSM", "orcid": "0000-0002-5294-7808", "researcher": {"href": "https://publications.scilifelab.se/researcher/894626ea67fd459eb08e4a9c4768fb09.json"}}, {"family": "Ross", "given": "Edith M", "initials": "EM"}, {"family": "Sanderson", "given": "Michael P", "initials": "MP"}, {"family": "Backman", "given": "Max", "initials": "M"}, {"family": "Botling", "given": "Johan", "initials": "J"}, {"family": "Brunnstr\u00f6m", "given": "Hans", "initials": "H", "orcid": "0000-0001-7402-138X", "researcher": {"href": "https://publications.scilifelab.se/researcher/618b52d539ee4e36ba7f9ce3b23f9d7f.json"}}, {"family": "Kurppa", "given": "Pinja", "initials": "P", "orcid": "0000-0003-3790-3986", "researcher": {"href": "https://publications.scilifelab.se/researcher/4f5b2c06aade428490f10e5eaf015d51.json"}}, {"family": "La Fleur", "given": "Linn\u00e9a", "initials": "L"}, {"family": "Strell", "given": "Carina", "initials": "C", "orcid": "0000-0002-3783-7256", "researcher": {"href": "https://publications.scilifelab.se/researcher/eb77b417ef2b479fb267969c3a557617.json"}}, {"family": "Wilm", "given": "Claudia", "initials": "C"}, {"family": "Zimmermann", "given": "Astrid", "initials": "A"}, {"family": "Esdar", "given": "Christina", "initials": "C"}, {"family": "Micke", "given": "Patrick", "initials": "P", "orcid": "0000-0003-1210-5961", "researcher": {"href": "https://publications.scilifelab.se/researcher/fc0cba74e74a4c39a8f96319cb9a3034.json"}}], "type": "journal article", "published": "2021-07-00", "journal": {"title": "Eur. J. Cancer", "issn": "1879-0852", "volume": "151", "issue": null, "pages": "136-149", "issn-l": "0959-8049"}, "abstract": "Amplification of fibroblast growth factor receptor 1 (FGFR1) in non-small cell lung cancer (NSCLC) has been considered as an actionable drug target. However, pan-FGFR tyrosine kinase inhibitors did not demonstrate convincing clinical efficacy in FGFR1-amplified NSCLC patients. This study aimed to characterise the molecular context of FGFR1 expression and to define biomarkers predictive of FGFR1 inhibitor response. In this study, 635 NSCLC samples were characterised for FGFR1 protein expression by immunohistochemistry and copy number gain (CNG) by in situ hybridisation (n = 298) or DNA microarray (n = 189). FGFR1 gene expression (n = 369) and immune cell profiles (n = 309) were also examined. Furthermore, gene expression, methylation and microRNA data from The Cancer Genome Atlas (TCGA) were compared. A panel of FGFR1-amplified NSCLC patient-derived xenograft (PDX) models were tested for response to the selective FGFR1 antagonist M6123. A minority of patients demonstrated FGFR1 CNG (10.5%) or increased FGFR1 mRNA (8.7%) and protein expression (4.4%). FGFR1 CNG correlated weakly with FGFR1 gene and protein expression. Tumours overexpressing FGFR1 protein were typically devoid of driver alterations (e.g. EGFR, KRAS) and showed reduced infiltration of T-lymphocytes and lower PD-L1 expression. Promoter methylation and microRNA were identified as regulators of FGFR1 expression in NSCLC and other cancers. Finally, NSCLC PDX models demonstrating FGFR1 amplification and FGFR1 protein overexpression were sensitive to M6123. The unique molecular and immune features of tumours with high FGFR1 expression provide a rationale to stratify patients in future clinical trials of FGFR1 pathway-targeting agents.", "doi": "10.1016/j.ejca.2021.04.005", "pmid": "33984662", "labels": {"NGI Stockholm (Genomics Production)": null, "NGI Stockholm (Genomics Applications)": null, "National Genomics Infrastructure": null}, "xrefs": [{"db": "pii", "key": "S0959-8049(21)00226-4"}], "notes": [], "created": "2021-06-09T12:16:54.718Z", "modified": "2021-11-10T12:23:43.669Z"}, {"entity": "publication", "iuid": "b9b71a4c6139494dbeedba7da68e5c49", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b9b71a4c6139494dbeedba7da68e5c49.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b9b71a4c6139494dbeedba7da68e5c49"}}, "title": "Mutation patterns in a population-based non-small cell lung cancer cohort and prognostic impact of concomitant mutations in KRAS and TP53 or STK11.", "authors": [{"family": "La Fleur", "given": "Linn\u00e9a", "initials": "L"}, {"family": "Falk-S\u00f6rqvist", "given": "Elin", "initials": "E"}, {"family": "Smeds", "given": "Patrik", "initials": "P"}, {"family": "Berglund", "given": "Anders", "initials": "A"}, {"family": "Sundstr\u00f6m", "given": "Magnus", "initials": "M"}, {"family": "Mattsson", "given": "Johanna Sm", "initials": "JS"}, {"family": "Brand\u00e9n", "given": "Eva", "initials": "E"}, {"family": "Koyi", "given": "Hirsh", "initials": "H", "orcid": "0000-0002-4960-1232", "researcher": {"href": "https://publications.scilifelab.se/researcher/952a87a3216c44baa33286c842c10d22.json"}}, {"family": "Isaksson", "given": "Johan", "initials": "J"}, {"family": "Brunnstr\u00f6m", "given": "Hans", "initials": "H"}, {"family": "Nilsson", "given": "Mats", "initials": "M", "orcid": "0000-0001-9985-0387", "researcher": {"href": "https://publications.scilifelab.se/researcher/197cf8ba83ba430f9712b2f4d94dc3e5.json"}}, {"family": "Micke", "given": "Patrick", "initials": "P", "orcid": "0000-0003-1210-5961", "researcher": {"href": "https://publications.scilifelab.se/researcher/fc0cba74e74a4c39a8f96319cb9a3034.json"}}, {"family": "Moens", "given": "Lotte", "initials": "L"}, {"family": "Botling", "given": "Johan", "initials": "J"}], "type": "journal article", "published": "2019-04-00", "journal": {"volume": "130", "issn": "1872-8332", "issue": null, "pages": "50-58", "title": "Lung Cancer", "issn-l": "0169-5002"}, "abstract": "Non-small cell lung cancer (NSCLC) is a heterogeneous disease with unique combinations of somatic molecular alterations in individual patients, as well as significant differences in populations across the world with regard to mutation spectra and mutation frequencies. Here we aim to describe mutational patterns and linked clinical parameters in a population-based NSCLC cohort.\n\nUsing targeted resequencing the mutational status of 82 genes was evaluated in a consecutive Swedish surgical NSCLC cohort, consisting of 352 patient samples from either fresh frozen or formalin fixed paraffin embedded (FFPE) tissues. The panel covers all exons of the 82 genes and utilizes reduced target fragment length and two-strand capture making it compatible with degraded FFPE samples.\n\nWe obtained a uniform sequencing coverage and mutation load across the fresh frozen and FFPE samples by adaption of sequencing depth and bioinformatic pipeline, thereby avoiding a technical bias between these two sample types. At large, the mutation frequencies resembled the frequencies seen in other western populations, except for a high frequency of KRAS hotspot mutations (43%) in adenocarcinoma patients. Worse overall survival was observed for adenocarcinoma patients with a mutation in either TP53, STK11 or SMARCA4. In the adenocarcinoma KRAS-mutated group poor survival appeared to be linked to concomitant TP53 or STK11 mutations, and not to KRAS mutation as a single aberration. Similar results were seen in the analysis of publicly available data from the cBioPortal. In squamous cell carcinoma a worse prognosis could be observed for patients with MLL2 mutations, while CSMD3 mutations were linked to a better prognosis.\n\nHere we have evaluated the mutational status of a NSCLC cohort. We could not confirm any survival impact of isolated driver mutations. Instead, concurrent mutations in TP53 and STK11 were shown to confer poor survival in the KRAS-positive adenocarcinoma subgroup.", "doi": "10.1016/j.lungcan.2019.01.003", "pmid": "30885352", "labels": {"National Genomics Infrastructure": "Service", "Clinical Genomics Uppsala": "Collaborative", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S0169-5002(19)30005-4"}], "notes": [], "created": "2019-11-29T13:21:46.345Z", "modified": "2024-01-16T13:48:44.581Z"}]}