{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T10:26:37Z","timestamp":1767176797599,"version":"build-2238731810"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1012847","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T00:00:00Z","timestamp":1746403200000}}],"reference-count":56,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T00:00:00Z","timestamp":1741305600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["ZIAHG200323"],"award-info":[{"award-number":["ZIAHG200323"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020038","name":"the Carlsberg Foundation","doi-asserted-by":"crossref","award":["CF21-0592"],"award-info":[{"award-number":["CF21-0592"]}],"id":[{"id":"10.13039\/100020038","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>\n                    Aberrant alternative splicing, prevalent in cancer, impacts various cancer hallmarks involving proliferation, angiogenesis, and invasion. Splicing disruption often results from somatic point mutations rewiring functional pathways to support cancer cell survival. We introduce iSoMAs (\n                    <jats:bold>iSo<\/jats:bold>\n                    form expression and somatic\n                    <jats:bold>M<\/jats:bold>\n                    utation\n                    <jats:bold>A<\/jats:bold>\n                    <jats:bold>s<\/jats:bold>\n                    sociation), an efficient computational pipeline leveraging principal component analysis technique, to explore how somatic mutations influence transcriptome-wide gene expression at the isoform level. Applying iSoMAs to 33 cancer types comprising 9,738 tumor samples in The Cancer Genome Atlas, we identified 908 somatically mutated genes significantly associated with altered isoform expression across three or more cancer types. Mutations linked to differential isoform expression occurred through both\n                    <jats:italic>cis<\/jats:italic>\n                    - and\n                    <jats:italic>trans<\/jats:italic>\n                    -acting mechanisms, involving well-known oncogenes\/suppressor genes, RNA binding protein and splicing factor genes. With wet-lab experiments, we verified direct association between\n                    <jats:italic>TP53<\/jats:italic>\n                    mutations and differential isoform expression in cell cycle genes. Additional iSoMAs genes have been validated in the literature with independent cohorts and\/or methods. Despite the complexity of cancer, iSoMAs attains computational efficiency via dimension reduction strategy and reveals critical associations between regulatory factors and transcriptional landscapes.\n                  <\/jats:p>","DOI":"10.1371\/journal.pcbi.1012847","type":"journal-article","created":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T13:21:17Z","timestamp":1741353677000},"page":"e1012847","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["iSoMAs: Finding isoform expression and somatic mutation associations in human 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