{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T18:59:14Z","timestamp":1775674754033,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1014134","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000}}],"reference-count":61,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Italian Association for Cancer Research","doi-asserted-by":"crossref","award":["24913"],"award-info":[{"award-number":["24913"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100005010","name":"Italian Association for Cancer Research","doi-asserted-by":"crossref","award":["27631"],"award-info":[{"award-number":["27631"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"crossref"}]},{"name":"European Union - NextGenerationEU","award":["J53D23015060001"],"award-info":[{"award-number":["J53D23015060001"]}]},{"name":"European Union - NextGenerationEU","award":["Project FAIR \u201cFuture Artificial Intelligence Research\u201d (DM 1555 of 11.10.2022)"],"award-info":[{"award-number":["Project FAIR \u201cFuture Artificial Intelligence Research\u201d (DM 1555 of 11.10.2022)"]}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>Genome aneuploidy, characterized by copy number variations (CNVs), profoundly alters gene expression in cancer through direct gene dosage effects and indirect compensatory regulatory mechanisms. However, existing differential gene expression (DGE) testing methods do not differentiate between these mechanisms, conflating all expression changes, limiting biological interpretability and obscuring key genes involved in tumor progression. To address this, we developed DeConveil, a computational framework that extends traditional DGE analysis by integrating CNV data. Using a generalized linear model with a negative binomial distribution, DeConveil models RNA-seq expression counts while accounting for copy number gene dosage effects. We proposed a more fine-grained gene decomposition into dosage-sensitive (DSGs), dosage-insensitive (DIGs), and dosage-compensated (DCGs), which explicitly de-couples changes due to CNVs and bona fide changes in transcriptional regulation. Analysis of TCGA datasets from aneuploid solid cancers resulted in notable reclassification of genes, refining and expanding upon the results from conventional methods. Functional enrichment analysis identified distinct biological roles for DSGs, DIGs, and DCGs in tumor progression, immune regulation, and cell adhesion. In a breast cancer case study, DeConveil\u2019s CN-aware analysis facilitated the identification of both known and novel prognostic biomarkers, including lncRNAs, linking gene expression signatures to survival outcomes. Utilizing these biomarkers for each gene group significantly improved patient risk stratification, yielding more accurate predictions compared to conventional methods. These results highlight DeConveil\u2019s ability to disentangle CNV-driven from regulatory transcriptional changes, enhancing gene classification and biomarker discovery. By improving transcriptomic analysis, DeConveil provides a powerful tool for cancer research, precision oncology, with potential applications in therapeutic target identification.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1014134","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T17:37:01Z","timestamp":1774633021000},"page":"e1014134","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Extending differential gene expression testing to handle genome aneuploidy in 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