{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T18:36:49Z","timestamp":1793126209770,"version":"4.5.0"},"update-to":[{"DOI":"10.1371\/journal.pgen.1012355","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T00:00:00Z","timestamp":1793059200000}}],"reference-count":65,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017192","name":"USC Norris Comprehensive Cancer Center","doi-asserted-by":"publisher","award":["P30CA014089"],"award-info":[{"award-number":["P30CA014089"]}],"id":[{"id":"10.13039\/100017192","id-type":"DOI","asserted-by":"publisher"}]},{"name":"USC Department of Translational Genomics Start-up Fund, University of Southern California","id":[{"id":"https:\/\/ror.org\/03taz7m60","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Department of Integrative Translational Sciences, Beckman Research Institute at City of Hope","id":[{"id":"https:\/\/ror.org\/05fazth07","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Richard Kronish"},{"name":"Richard Kronish"}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>\n                    High-grade serous ovarian cancer (HGSOC) is characterized by remarkable intratumoral heterogeneity and variable tissue architectures, dictating differential therapeutic responses. Although\n                    <jats:italic>BRCA1\/2<\/jats:italic>\n                    mutations correlate with improved responses to DNA-damaging agents, how BRCA genotype shapes the tumor immune microenvironment (TIME) remains incompletely understood. Here, we integrated whole exome sequencing, total RNA sequencing and spatial transcriptomics to profile a cohort of BRCA-mutated (BRCA-MT) and non-BRCA-mutated (BRCA-WT) HGSOC tumors. While bulk transcriptomics highlighted global phenotypic shifts, suggesting a more pro-inflammatory milieu in BRCA-MT tumors, spatially resolved analysis revealed how these differences manifest within specific tissue architectures. Integrated clustering revealed recurrent spatial transcriptional states across genotypes. Specifically, we identified a transcriptionally distinct immune-enriched region (IC7) characterized by low tumor purity, interferon signaling, and antigen-presentation programs. Reference-based RCTD deconvolution provided orthogonal computational support that IC7 was enriched for T\/NK and dendritic cells relative to non-IC7 regions. At the patient level, the functional state of IC7 was highly BRCA-dependent: BRCA-MT tumors exhibited stronger enrichment of interferon-\u03b1\/\u03b3 responses and inflammatory signaling than BRCA-WT tumors. Exploratory CellChat analysis further suggested genotype-associated differences in predicted immune-related signaling. We also identify a conserved structural interface between CAF-like region (IC3) and macrophage-rich region (IC4), accompanied by a predicted CXCL12\u2013CXCR4 chemokine recruitment axis. Taken together, these findings support a model in which BRCA mutation status is associated with functional differences within broadly conserved spatial regions, rather than extensive reorganization of the overall spatial architecture. This spatially resolved framework identifies BRCA-associated immune transcriptional patterns in HGSOC and provides a basis for future mechanistic validation.\n                  <\/jats:p>","DOI":"10.1371\/journal.pgen.1012355","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T17:41:10Z","timestamp":1792690870000},"page":"e1012355","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi-omics analysis of high-grade serous ovarian cancers reveals heterogeneity and distinct immunological patterns based upon clinico-genomic status"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7026-9386","authenticated-orcid":true,"given":"Jing","family":"Qian","sequence":"first","affiliation":[{"name":"University of Southern California","place":["Los Angeles, California, United States of America"],"department":["Department of Cancer Biology, Keck School of Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4754-9311","authenticated-orcid":true,"given":"Rania","family":"Bassiouni","sequence":"additional","affiliation":[{"name":"Beckman Research Institute, City of Hope","place":["Duarte, California, United States of America"],"department":["Department of Integrative Translational Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6124-9681","authenticated-orcid":true,"given":"Yuxin","family":"Jin","sequence":"additional","affiliation":[{"name":"Beckman Research Institute, City of Hope","place":["Duarte, California, United States of America"],"department":["Department of Integrative Translational Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seeta","family":"Rajpara","sequence":"additional","affiliation":[{"name":"University of Southern California","place":["Los Angeles, California, United States of America"],"department":["Department of Cancer Biology, Keck School of Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Neuman","sequence":"additional","affiliation":[{"name":"Los Angeles General Medical Center","place":["Los Angeles, California, United States of America"],"department":["Department of Obstetrics and Gynecology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2825-2157","authenticated-orcid":true,"given":"Varun U.","family":"Khetan","sequence":"additional","affiliation":[{"name":"Los Angeles General Medical Center","place":["Los Angeles, California, United States of America"],"department":["Department of Obstetrics and Gynecology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bodour","family":"Salhia","sequence":"additional","affiliation":[{"name":"University of Southern California","place":["Los Angeles, California, United States of America"],"department":["Department of Cancer Biology, Keck School of Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2040-1955","authenticated-orcid":true,"given":"David W.","family":"Craig","sequence":"additional","affiliation":[{"name":"Beckman Research Institute, City of Hope","place":["Duarte, California, United States of America"],"department":["Department of Integrative Translational Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3006-4107","authenticated-orcid":true,"given":"Joseph W.","family":"Carlson","sequence":"additional","affiliation":[{"name":"City of Hope","place":["Duarte, California, United States of America"],"department":["Department of Pathology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynda D.","family":"Roman","sequence":"additional","affiliation":[{"name":"University of Southern California","place":["Los Angeles, California, United States of America"],"department":["Department of Obstetrics and Gynecology, Keck School of Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6862-2821","authenticated-orcid":true,"given":"John D.","family":"Carpten","sequence":"additional","affiliation":[{"name":"Beckman Research Institute, City of Hope","place":["Duarte, California, United States of America"],"department":["Department of Integrative Translational Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,10,22]]},"reference":[{"key":"pgen.1012355.ref001","first-page":"10","article-title":"Cancer statistics, 2025","volume":"75","author":"RL Siegel","year":"2025","journal-title":"Ca"},{"issue":"1","key":"pgen.1012355.ref002","doi-asserted-by":"crossref","first-page":"12","DOI":"10.3390\/diagnostics7010012","article-title":"Subtypes of Ovarian Cancer and Ovarian Cancer Screening","volume":"7","author":"M Koshiyama","year":"2017","journal-title":"Diagnostics (Basel)"},{"key":"pgen.1012355.ref003","article-title":"Treatment of epithelial ovarian cancer","author":"L Kuroki","year":"2020","journal-title":"BMJ"},{"key":"pgen.1012355.ref004","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1038\/nature10166","article-title":"Integrated genomic analyses of ovarian carcinoma","volume":"474","author":"The Cancer Genome Atlas Research Network","year":"2011","journal-title":"Nature"},{"issue":"26","key":"pgen.1012355.ref005","doi-asserted-by":"crossref","first-page":"2495","DOI":"10.1056\/NEJMoa1810858","article-title":"Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer","volume":"379","author":"K Moore","year":"2018","journal-title":"N Engl J Med"},{"issue":"11","key":"pgen.1012355.ref006","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1038\/nm.3369","article-title":"Mechanisms of resistance to therapies targeting BRCA-mutant cancers","volume":"19","author":"CJ Lord","year":"2013","journal-title":"Nat Med"},{"issue":"7553","key":"pgen.1012355.ref007","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/nature14410","article-title":"Whole-genome characterization of chemoresistant ovarian cancer","volume":"521","author":"A-M Patch","year":"2015","journal-title":"Nature"},{"issue":"10","key":"pgen.1012355.ref008","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1038\/ni.3558","article-title":"Regulation and function of the cGAS-STING pathway of cytosolic DNA sensing","volume":"17","author":"Q Chen","year":"2016","journal-title":"Nat Immunol"},{"issue":"1","key":"pgen.1012355.ref009","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a001008","article-title":"TP53 mutations in human cancers: origins, consequences, and clinical use","volume":"2","author":"M Olivier","year":"2010","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"pgen.1012355.ref010","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1097\/PGP.0000000000000207","article-title":"Molecular alterations of TP53 are a defining feature of ovarian high-grade serous carcinoma: a rereview of cases lacking TP53 mutations in the Cancer Genome Atlas ovarian study","volume":"35","author":"R Vang","year":"2016","journal-title":"Int J Gynecol Pathol Off J Int Soc Gynecol Pathol"},{"issue":"7793","key":"pgen.1012355.ref011","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/s41586-020-1943-3","article-title":"The repertoire of mutational signatures in human cancer","volume":"578","author":"LB Alexandrov","year":"2020","journal-title":"Nature"},{"issue":"7463","key":"pgen.1012355.ref012","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/nature12477","article-title":"Signatures of mutational processes in human cancer","volume":"500","author":"LB Alexandrov","year":"2013","journal-title":"Nature"},{"key":"pgen.1012355.ref013","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1038\/s41523-018-0066-6","article-title":"Migrating the SNP array-based homologous recombination deficiency measures to next generation sequencing data of breast cancer","volume":"4","author":"Z Sztupinszki","year":"2018","journal-title":"NPJ Breast Cancer"},{"issue":"15","key":"pgen.1012355.ref014","doi-asserted-by":"crossref","first-page":"3764","DOI":"10.1158\/1078-0432.CCR-15-2477","article-title":"Homologous Recombination Deficiency (HRD) Score Predicts Response to Platinum-Containing Neoadjuvant Chemotherapy in Patients with Triple-Negative Breast Cancer","volume":"22","author":"ML Telli","year":"2016","journal-title":"Clin Cancer Res"},{"issue":"7","key":"pgen.1012355.ref015","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1038\/s41587-019-0114-2","article-title":"Determining cell type abundance and expression from bulk tissues with digital cytometry","volume":"37","author":"AM Newman","year":"2019","journal-title":"Nat Biotechnol"},{"issue":"7","key":"pgen.1012355.ref016","doi-asserted-by":"crossref","DOI":"10.1093\/gigascience\/giy083","article-title":"Clustering trees: a visualization for evaluating clusterings at multiple resolutions","volume":"7","author":"L Zappia","year":"2018","journal-title":"Gigascience"},{"issue":"8","key":"pgen.1012355.ref017","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.abm1831","article-title":"Longitudinal single-cell RNA-seq analysis reveals stress-promoted chemoresistance in metastatic ovarian cancer","volume":"8","author":"K Zhang","year":"2022","journal-title":"Sci Adv"},{"issue":"3","key":"pgen.1012355.ref018","doi-asserted-by":"crossref","DOI":"10.1016\/j.cell.2019.05.054","article-title":"Lipid-Associated Macrophages Control Metabolic Homeostasis in a Trem2-Dependent Manner","volume":"178","author":"DA Jaitin","year":"2019","journal-title":"Cell"},{"issue":"7965","key":"pgen.1012355.ref019","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1038\/s41586-023-06130-4","article-title":"Hallmarks of transcriptional intratumour heterogeneity across a thousand tumours","volume":"618","author":"A Gavish","year":"2023","journal-title":"Nature"},{"issue":"1","key":"pgen.1012355.ref020","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1038\/s41467-021-21246-9","article-title":"Inference and analysis of cell-cell communication using CellChat","volume":"12","author":"S Jin","year":"2021","journal-title":"Nat Commun"},{"issue":"16","key":"pgen.1012355.ref021","doi-asserted-by":"crossref","first-page":"5522","DOI":"10.1158\/0008-5472.CAN-10-3143","article-title":"CXCL12\/CXCR4 blockade induces multimodal antitumor effects that prolong survival in an immunocompetent mouse model of ovarian cancer","volume":"71","author":"E Righi","year":"2011","journal-title":"Cancer Res"},{"key":"pgen.1012355.ref022","doi-asserted-by":"crossref","first-page":"3474","DOI":"10.1158\/1078-0432.CCR-13-0066","article-title":"Nonequivalent gene expression and copy number alterations in high-grade serous ovarian cancers with BRCA1 and BRCA2 mutations","volume":"19","author":"J George","year":"2013","journal-title":"Clin Cancer Res"},{"issue":"27","key":"pgen.1012355.ref023","doi-asserted-by":"crossref","first-page":"43653","DOI":"10.18632\/oncotarget.17613","article-title":"Biological and clinical evidence for somatic mutations in BRCA1 and BRCA2 as predictive markers for olaparib response in high-grade serous ovarian cancers in the maintenance setting","volume":"8","author":"BA Dougherty","year":"2017","journal-title":"Oncotarget"},{"issue":"1","key":"pgen.1012355.ref024","doi-asserted-by":"crossref","first-page":"3970","DOI":"10.1038\/s41467-018-05564-z","article-title":"Methylation of all BRCA1 copies predicts response to the PARP inhibitor rucaparib in ovarian carcinoma","volume":"9","author":"O Kondrashova","year":"2018","journal-title":"Nat Commun"},{"key":"pgen.1012355.ref025","doi-asserted-by":"crossref","first-page":"115299","DOI":"10.1016\/j.ejca.2025.115299","article-title":"Somatic BRCA1\/2 mutations are associated with a similar survival advantage to their germline counterparts in tubo-ovarian high grade serous carcinoma","volume":"219","author":"RL Hollis","year":"2025","journal-title":"Eur J Cancer"},{"issue":"1","key":"pgen.1012355.ref026","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1158\/0008-5472.CAN-22-2682","article-title":"Spatial Transcriptomic Analysis of a Diverse Patient Cohort Reveals a Conserved Architecture in Triple-Negative Breast Cancer","volume":"83","author":"R Bassiouni","year":"2023","journal-title":"Cancer Res"},{"issue":"22","key":"pgen.1012355.ref027","doi-asserted-by":"crossref","first-page":"5493","DOI":"10.1158\/1078-0432.CCR-18-1731","article-title":"Neoantigens in Ovarian Cancer: Embarrassment of Riches or Needles in a Haystack?","volume":"24","author":"IA McNeish","year":"2018","journal-title":"Clin Cancer Res"},{"issue":"11","key":"pgen.1012355.ref028","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1016\/S1470-2045(16)30376-X","article-title":"Overall survival in patients with platinum-sensitive recurrent serous ovarian cancer receiving olaparib maintenance monotherapy: an updated analysis from a randomised, placebo-controlled, double-blind, phase 2 trial","volume":"17","author":"JA Ledermann","year":"2016","journal-title":"Lancet Oncol"},{"issue":"12","key":"pgen.1012355.ref029","doi-asserted-by":"crossref","first-page":"13587","DOI":"10.18632\/oncotarget.7277","article-title":"Association and prognostic significance of BRCA1\/2-mutation status with neoantigen load, number of tumor-infiltrating lymphocytes and expression of PD-1\/PD-L1 in high grade serous ovarian cancer","volume":"7","author":"KC Strickland","year":"2016","journal-title":"Oncotarget"},{"issue":"2","key":"pgen.1012355.ref030","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.1001789","article-title":"Spatial and temporal heterogeneity in high-grade serous ovarian cancer: a phylogenetic analysis","volume":"12","author":"RF Schwarz","year":"2015","journal-title":"PLoS Med"},{"issue":"6","key":"pgen.1012355.ref031","doi-asserted-by":"crossref","first-page":"101055","DOI":"10.1016\/j.xcrm.2023.101055","article-title":"Spatial and temporal intra-tumoral heterogeneity in advanced HGSOC: Implications for surgical and clinical outcomes","volume":"4","author":"P Cunnea","year":"2023","journal-title":"Cell Rep Med"},{"key":"pgen.1012355.ref032","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1158\/0008-5472.CAN-25-3189","article-title":"Integrated spatial analysis reveals the molecular landscape of ovarian precancerous lesions","volume":"86","author":"TY Chang","year":"2026","journal-title":"Cancer Research"},{"issue":"1","key":"pgen.1012355.ref033","doi-asserted-by":"crossref","first-page":"2860","DOI":"10.1038\/s41467-024-47271-y","article-title":"Spatial transcriptomics reveals discrete tumour microenvironments and autocrine loops within ovarian cancer subclones","volume":"15","author":"E Denisenko","year":"2024","journal-title":"Nat Commun"},{"issue":"12","key":"pgen.1012355.ref034","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.1158\/1541-7786.MCR-21-0411","article-title":"The Spatial Context of Tumor-Infiltrating Immune Cells Associates with Improved Ovarian Cancer Survival","volume":"19","author":"B Steinhart","year":"2021","journal-title":"Mol Cancer Res"},{"issue":"11","key":"pgen.1012355.ref035","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1016\/j.tem.2024.04.009","article-title":"Lipid-associated macrophages between aggravation and alleviation of metabolic diseases","volume":"35","author":"R Xu","year":"2024","journal-title":"Trends Endocrinol Metab"},{"issue":"8","key":"pgen.1012355.ref036","doi-asserted-by":"crossref","DOI":"10.1016\/j.immuni.2021.07.007","article-title":"Cross-tissue single-cell landscape of human monocytes and macrophages in health and disease","volume":"54","author":"K Mulder","year":"2021","journal-title":"Immunity"},{"issue":"18","key":"pgen.1012355.ref037","doi-asserted-by":"crossref","first-page":"3291","DOI":"10.1158\/0008-5472.CAN-22-1427","article-title":"Lipid-Associated Macrophages Are Induced by Cancer-Associated Fibroblasts and Mediate Immune Suppression in Breast Cancer","volume":"82","author":"E Timperi","year":"2022","journal-title":"Cancer Res"},{"issue":"10","key":"pgen.1012355.ref038","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1038\/s41590-024-01943-5","article-title":"Mapping spatial organization and genetic cell-state regulators to target immune evasion in ovarian cancer","volume":"25","author":"CY Yeh","year":"2024","journal-title":"Nat Immunol"},{"issue":"23","key":"pgen.1012355.ref039","doi-asserted-by":"crossref","first-page":"5242","DOI":"10.1158\/1078-0432.CCR-24-1690","article-title":"At the Interface of Tumor-Associated Macrophages and Fibroblasts: Immune-Suppressive Networks and Emerging Exploitable Targets","volume":"30","author":"E Timperi","year":"2024","journal-title":"Clin Cancer Res"},{"issue":"1","key":"pgen.1012355.ref040","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"A Dobin","year":"2013","journal-title":"Bioinformatics"},{"issue":"4","key":"pgen.1012355.ref041","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/nmeth.4197","article-title":"Salmon provides fast and bias-aware quantification of transcript expression","volume":"14","author":"R Patro","year":"2017","journal-title":"Nat Methods"},{"issue":"7","key":"pgen.1012355.ref042","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","article-title":"featureCounts: an efficient general purpose program for assigning sequence reads to genomic features","volume":"30","author":"Y Liao","year":"2014","journal-title":"Bioinformatics"},{"issue":"9","key":"pgen.1012355.ref043","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1101\/gr.107524.110","article-title":"The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data","volume":"20","author":"A McKenna","year":"2010","journal-title":"Genome Res"},{"issue":"16","key":"pgen.1012355.ref044","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The Sequence Alignment\/Map format and SAMtools","volume":"25","author":"H Li","year":"2009","journal-title":"Bioinformatics"},{"key":"pgen.1012355.ref045","volume-title":"Haplotype-based variant detection from short-read sequencing","author":"E Garrison","year":"2012"},{"issue":"8","key":"pgen.1012355.ref046","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1038\/s41592-018-0051-x","article-title":"Strelka2: fast and accurate calling of germline and somatic variants","volume":"15","author":"S Kim","year":"2018","journal-title":"Nat Methods"},{"issue":"2","key":"pgen.1012355.ref047","doi-asserted-by":"crossref","first-page":"80","DOI":"10.4161\/fly.19695","article-title":"A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff","volume":"6","author":"P Cingolani","year":"2012","journal-title":"Fly"},{"key":"pgen.1012355.ref048","doi-asserted-by":"crossref","first-page":"35","DOI":"10.3389\/fgene.2012.00035","article-title":"Using Drosophila melanogaster as a Model for Genotoxic Chemical Mutational Studies with a New Program, SnpSift","volume":"3","author":"P Cingolani","year":"2012","journal-title":"Front Genet"},{"key":"pgen.1012355.ref049","volume-title":"Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM","author":"H Li","year":"2013"},{"issue":"3","key":"pgen.1012355.ref050","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/nbt.2514","article-title":"Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples","volume":"31","author":"K Cibulskis","year":"2013","journal-title":"Nat Biotechnol"},{"key":"pgen.1012355.ref051","doi-asserted-by":"crossref","DOI":"10.1186\/s13059-016-0974-4","article-title":"The Ensembl Variant Effect Predictor","volume":"17","author":"W McLaren","year":"2016","journal-title":"Genome Biol"},{"issue":"11","key":"pgen.1012355.ref052","article-title":"Uncovering novel mutational signatures by de novo extraction with SigProfilerExtractor","volume":"2","author":"SMA Islam","year":"2022","journal-title":"Cell Genom"},{"issue":"11","key":"pgen.1012355.ref053","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1101\/gr.239244.118","article-title":"Maftools: efficient and comprehensive analysis of somatic variants in cancer","volume":"28","author":"A Mayakonda","year":"2018","journal-title":"Genome Res"},{"issue":"1","key":"pgen.1012355.ref054","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1093\/annonc\/mdu479","article-title":"Sequenza: allele-specific copy number and mutation profiles from tumor sequencing data","volume":"26","author":"F Favero","year":"2015","journal-title":"Ann Oncol"},{"issue":"12","key":"pgen.1012355.ref055","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"MI Love","year":"2014","journal-title":"Genome Biol"},{"issue":"6","key":"pgen.1012355.ref056","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.cels.2015.12.004","article-title":"The Molecular Signatures Database (MSigDB) hallmark gene set collection","volume":"1","author":"A Liberzon","year":"2015","journal-title":"Cell Syst"},{"issue":"43","key":"pgen.1012355.ref057","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"A Subramanian","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"pgen.1012355.ref058","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1186\/s13059-017-1349-1","article-title":"xCell: digitally portraying the tissue cellular heterogeneity landscape","volume":"18","author":"D Aran","year":"2017","journal-title":"Genome Biol"},{"issue":"21","key":"pgen.1012355.ref059","doi-asserted-by":"crossref","first-page":"4394","DOI":"10.1093\/bioinformatics\/btz235","article-title":"HLA*LA-HLA typing from linearly projected graph alignments","volume":"35","author":"AT Dilthey","year":"2019","journal-title":"Bioinformatics"},{"issue":"3","key":"pgen.1012355.ref060","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1158\/2326-6066.CIR-19-0401","article-title":"pVACtools: A Computational Toolkit to Identify and Visualize Cancer Neoantigens","volume":"8","author":"J Hundal","year":"2020","journal-title":"Cancer Immunol Res"},{"issue":"13","key":"pgen.1012355.ref061","article-title":"Integrated analysis of multimodal single-cell data","volume":"184","author":"Y Hao","year":"2021","journal-title":"Cell"},{"issue":"1","key":"pgen.1012355.ref062","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1186\/s13059-019-1874-1","article-title":"Normalization and variance stabilization of single-cell RNA-seq data using regularized negative binomial regression","volume":"20","author":"C Hafemeister","year":"2019","journal-title":"Genome Biol"},{"key":"pgen.1012355.ref063","doi-asserted-by":"crossref","first-page":"2612","DOI":"10.1038\/ncomms3612","article-title":"Inferring tumour purity and stromal and immune cell admixture from expression data","volume":"4","author":"K Yoshihara","year":"2013","journal-title":"Nat Commun"},{"issue":"7","key":"pgen.1012355.ref064","doi-asserted-by":"crossref","DOI":"10.1016\/j.cell.2019.05.031","article-title":"Comprehensive Integration of Single-Cell Data","volume":"177","author":"T Stuart","year":"2019","journal-title":"Cell"},{"issue":"4","key":"pgen.1012355.ref065","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/s41587-021-00830-w","article-title":"Robust decomposition of cell type mixtures in spatial transcriptomics","volume":"40","author":"DM Cable","year":"2022","journal-title":"Nat Biotechnol"}],"updated-by":[{"DOI":"10.1371\/journal.pgen.1012355","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T00:00:00Z","timestamp":1793059200000}}],"container-title":["PLOS Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1012355","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T18:22:43Z","timestamp":1793125363000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1012355"}},"subtitle":[],"editor":[{"given":"Yan","family":"Tang","sequence":"first","affiliation":[{"name":"Brigham and Women\u2019s Hospital","place":["UNITED STATES OF AMERICA"]}],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,10,22]]},"references-count":65,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,10,22]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pgen.1012355","relation":{},"ISSN":["1553-7404"],"issn-type":[{"value":"1553-7404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,22]]}}}