{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T17:45:37Z","timestamp":1770745537806,"version":"3.49.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2021,3,31]],"date-time":"2021-03-31T00:00:00Z","timestamp":1617148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000071","name":"NICHD","doi-asserted-by":"publisher","award":["K08 HD092610"],"award-info":[{"award-number":["K08 HD092610"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"NIMH","doi-asserted-by":"publisher","award":["R01MH118239"],"award-info":[{"award-number":["R01MH118239"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"NIMH","doi-asserted-by":"publisher","award":["R01MH114593"],"award-info":[{"award-number":["R01MH114593"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"NIMH","doi-asserted-by":"publisher","award":["R01MH110531"],"award-info":[{"award-number":["R01MH110531"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009670","name":"NARSAD","doi-asserted-by":"publisher","award":["28599"],"award-info":[{"award-number":["28599"]}],"id":[{"id":"10.13039\/100009670","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,9,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Motivation: Rare variant-based analyses are beginning to identify risk genes for neuropsychiatric disorders and other diseases. However, the identified genes only account for a fraction of predicted causal genes. Recent studies have shown that rare damaging variants are significantly enriched in specific gene-sets. Methods which are able to jointly model rare variants and gene-sets to identify enriched gene-sets and use these enriched gene-sets to prioritize additional risk genes could improve understanding of the genetic architecture of diseases.<\/jats:p><jats:p>Results: We propose DECO (Integrated analysis of de novo mutations, rare case\/control variants and omics information via gene-sets), an integrated method for rare-variant and gene-set analysis. The method can (i) test the enrichment of gene-sets directly within the statistical model, and (ii) use enriched gene-sets to rank existing genes and prioritize additional risk genes for tested disorders. In simulations, DECO performs better than a homologous method that uses only variant data. To demonstrate the application of the proposed protocol, we have applied this approach to rare-variant datasets of schizophrenia. Compared with a method which only uses variant information, DECO is able to prioritize additional risk genes.<\/jats:p><jats:p>Availability: DECO can be used to analyze rare-variants and biological pathways or cell types for any disease. The package is available on Github https:\/\/github.com\/hoangtn\/DECO.<\/jats:p>","DOI":"10.1093\/bib\/bbab067","type":"journal-article","created":{"date-parts":[[2021,2,10]],"date-time":"2021-02-10T20:13:50Z","timestamp":1612988030000},"source":"Crossref","is-referenced-by-count":6,"title":["DECO: a framework for jointly analyzing<i>de novo<\/i>and rare case\/control variants, and biological pathways"],"prefix":"10.1093","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6910-7269","authenticated-orcid":false,"given":"Tan-Hoang","family":"Nguyen","sequence":"first","affiliation":[{"name":"Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"He","sequence":"additional","affiliation":[{"name":"The Department of Human Genetics, University of Chicago, IL 60637, USA; Grossman Institute for Neuroscience, Quantitative Biology and Human Behavior, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruth C","family":"Brown","sequence":"additional","affiliation":[{"name":"Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bradley T","family":"Webb","sequence":"additional","affiliation":[{"name":"Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth S","family":"Kendler","sequence":"additional","affiliation":[{"name":"Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vladimir I","family":"Vladimirov","sequence":"additional","affiliation":[{"name":"Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA; Department of Psychiatry & Behavioral Sciences, College of Medicine, Texas A&M University, College Station, TX, USA; and the Lieber Institute for Brain Development, Baltimore, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brien P","family":"Riley","sequence":"additional","affiliation":[{"name":"Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silviu-Alin","family":"Bacanu","sequence":"additional","affiliation":[{"name":"Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, 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