{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T13:06:35Z","timestamp":1781701595200,"version":"3.54.5"},"reference-count":67,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T00:00:00Z","timestamp":1626393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100008510","name":"University of Maryland","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008510","id-type":"DOI","asserted-by":"crossref"}]},{"name":"KVPY Fellowship, Department of Science and Technology (DST), India"},{"name":"Intramural Research Program, National Cancer Institute, Center for Cancer Research, NIH"},{"name":"Intramural Research Program, National Cancer Institute, Center for Cancer Research, NIH"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>Knowledge of genes that are critical to a tissue\u2019s function remains difficult to ascertain and presents a major bottleneck toward a mechanistic understanding of genotype-phenotype links. Here, we present the first machine learning model\u2013FUGUE\u2013combining transcriptional and network features, to predict tissue-relevant genes across 30 human tissues. FUGUE achieves an average cross-validation auROC of 0.86 and auPRC of 0.50 (expected 0.09). In independent datasets, FUGUE accurately distinguishes tissue or cell type-specific genes, significantly outperforming the conventional metric based on tissue-specific expression alone. Comparison of tissue-relevant transcription factors across tissue recapitulate their developmental relationships. Interestingly, the tissue-relevant genes cluster on the genome within topologically associated domains and furthermore, are highly enriched for differentially expressed genes in the corresponding cancer type. We provide the prioritized gene lists in 30 human tissues and an open-source software to prioritize genes in a novel context given multi-sample transcriptomic data.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1009194","type":"journal-article","created":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T13:25:47Z","timestamp":1626441947000},"page":"e1009194","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":13,"title":["Prioritizing and characterizing functionally relevant genes across human tissues"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5380-1413","authenticated-orcid":true,"given":"Gowthami","family":"Somepalli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7771-5894","authenticated-orcid":true,"given":"Sarthak","family":"Sahoo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6087-7240","authenticated-orcid":true,"given":"Arashdeep","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9603-7569","authenticated-orcid":true,"given":"Sridhar","family":"Hannenhalli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,7,16]]},"reference":[{"key":"pcbi.1009194.ref001","article-title":"The y-ome defines the 35% of Escherichia coli genes that lack experimental evidence of function","author":"S Ghatak","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"pcbi.1009194.ref002","article-title":"BRCA1, hormone, and tissue-specific tumor suppression","author":"Y. 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