{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,15]],"date-time":"2025-11-15T16:33:05Z","timestamp":1763224385016,"version":"3.45.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:00:00Z","timestamp":1760054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AG071170","R01 MH126449"],"award-info":[{"award-number":["R01 AG071170","R01 MH126449"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>Differential co-expression analysis (DCA) aims to identify genes in a pathway whose shared expression depends on a risk factor. While DCA provides insights into the biological activity of diseases, existing methods are limited to categorical risk factors and\/or suffer from bias due to batch and variance-specific effects. We propose a new framework, Kernel-based DCA (KDCA), that harnesses correlation patterns between genes in a pathway to detect differential co-expression arising from general (i.e. continuous, discrete, or categorical) risk factors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Using various simulated pathway architectures, we find that KDCA accounts for common sources of bias to control the type I error rate while substantially increasing the power compared to the standard eigengene approach. We then applied KDCA to The Cancer Genome Atlas thyroid data set and found several differentially co-expressed pathways by age of diagnosis and BRAF mutation status that were undetected by the eigengene method. Collectively, our results demonstrate that KDCA is a powerful testing framework that expands DCA applications in expression studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>KDCA is publicly available in the R package kdca. The package can be downloaded at https:\/\/github.com\/ajbass\/kdca.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btaf565","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T12:19:30Z","timestamp":1759925970000},"source":"Crossref","is-referenced-by-count":0,"title":["A powerful framework for differential co-expression analysis of general risk factors"],"prefix":"10.1093","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7762-4055","authenticated-orcid":false,"given":"Andrew J","family":"Bass","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Cambridge , Cambridge CB2 0AW,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6394-6731","authenticated-orcid":false,"given":"David J","family":"Cutler","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Emory University , Atlanta, GA 30322,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9647-9738","authenticated-orcid":false,"given":"Michael P","family":"Epstein","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Emory University , Atlanta, GA 30322,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,10,10]]},"reference":[{"key":"2025111511265215000_btaf565-B1","doi-asserted-by":"crossref","first-page":"4982","DOI":"10.3390\/cancers15204982","article-title":"The multifaceted functions of prion protein (PRPC) in cancer","volume":"15","author":"Abi Nahed","year":"2023","journal-title":"Cancers (Basel)"},{"key":"2025111511265215000_btaf565-B2","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/j.cell.2014.09.050","article-title":"Integrated genomic characterization of papillary thyroid carcinoma","volume":"159","author":"Agrawal","year":"2014","journal-title":"Cell"},{"key":"2025111511265215000_btaf565-B3","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1016\/j.ajhg.2014.03.016","article-title":"Maximizing the power of principal-component analysis of correlated phenotypes in genome-wide association studies","volume":"94","author":"Aschard","year":"2014","journal-title":"Am J Hum Genet"},{"key":"2025111511265215000_btaf565-B4","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/s13073-024-01329-0","article-title":"Identifying latent genetic interactions in genome-wide association studies using multiple traits","volume":"16","author":"Bass","year":"2024","journal-title":"Genome Med"},{"key":"2025111511265215000_btaf565-B5","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.ajhg.2016.01.017","article-title":"A statistical approach for testing cross-phenotype effects of rare variants","volume":"98","author":"Broadaway","year":"2016","journal-title":"Am J Hum Genet"},{"key":"2025111511265215000_btaf565-B6","doi-asserted-by":"crossref","first-page":"2345","DOI":"10.1038\/s41467-021-22560-y","article-title":"An integrative analysis of the age-associated multi-omic landscape across cancers","volume":"12","author":"Chatsirisupachai","year":"2021","journal-title":"Nat Commun"},{"key":"2025111511265215000_btaf565-B7","doi-asserted-by":"crossref","first-page":"2780","DOI":"10.1093\/bioinformatics\/btp502","article-title":"Statistical methods for gene set co-expression analysis","volume":"25","author":"Choi","year":"2009","journal-title":"Bioinformatics"},{"key":"2025111511265215000_btaf565-B8","doi-asserted-by":"crossref","first-page":"e71","DOI":"10.1093\/nar\/gkv1507","article-title":"TCGAbiolinks: an R\/Bioconductor package for integrative analysis of TCGA data","volume":"44","author":"Colaprico","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"2025111511265215000_btaf565-B9","first-page":"323","article-title":"Algorithm AS 155: the distribution of a linear combination of \u03c72 random variables","volume":"29","author":"Davies","year":"1980","journal-title":"J Roy Stat Soc. 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