{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:25:26Z","timestamp":1769127926296,"version":"3.49.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T00:00:00Z","timestamp":1641513600000},"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\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["317\/19"],"award-info":[{"award-number":["317\/19"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Edmond J. Safra Center for Bioinformatics at Tel-Aviv University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,3,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Motivation<\/jats:title><jats:p>The distinct functionalities of human tissues and cell types underlie complex phenotype\u2013genotype relationships, yet often remain elusive. Harnessing the multitude of bulk and single-cell human transcriptomes while focusing on processes can help reveal these distinct functionalities.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The Tissue-Process Activity (TiPA) method aims to identify processes that are preferentially active or under-expressed in specific contexts, by comparing the expression levels of process genes between contexts. We tested TiPA on 1579 tissue-specific processes and bulk tissue transcriptomes, finding that it performed better than another method. Next, we used TiPA to ask whether the activity of certain processes could underlie the tissue-specific manifestation of 1233 hereditary diseases. We found that 21% of the disease-causing genes indeed participated in such processes, thereby illuminating their genotype\u2013phenotype relationships. Lastly, we applied TiPA to single-cell transcriptomes of 108 human cell types, revealing that process activities often match cell-type identities and can thus aid annotation efforts. Hence, differential activity of processes can highlight the distinct functionality of tissues and cells in a robust and meaningful manner.<\/jats:p><\/jats:sec><jats:sec><jats:title>Availability and implementation<\/jats:title><jats:p>TiPA code is available in GitHub (https:\/\/github.com\/moranshar\/TiPA). In addition, all data are available as part of the Supplementary Material.<\/jats:p><\/jats:sec><jats:sec><jats:title>Supplementary information<\/jats:title><jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p><\/jats:sec>","DOI":"10.1093\/bioinformatics\/btab883","type":"journal-article","created":{"date-parts":[[2022,1,2]],"date-time":"2022-01-02T20:06:25Z","timestamp":1641153985000},"page":"1584-1592","source":"Crossref","is-referenced-by-count":12,"title":["The differential activity of biological processes in tissues and cell subsets can illuminate disease-related processes and cell-type identities"],"prefix":"10.1093","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1478-8719","authenticated-orcid":false,"given":"Moran","family":"Sharon","sequence":"first","affiliation":[{"name":"Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev , Beer Sheva, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ekaterina","family":"Vinogradov","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev , Beer Sheva, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chanan M","family":"Argov","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev , Beer Sheva, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Or","family":"Lazarescu","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev , Beer Sheva, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yazeed","family":"Zoabi","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Idan","family":"Hekselman","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev , Beer Sheva, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esti","family":"Yeger-Lotem","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev , Beer Sheva, Israel"},{"name":"The National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev , Beer Sheva, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,1,7]]},"reference":[{"key":"2023020108580752100_btab883-B1","doi-asserted-by":"crossref","first-page":"305","DOI":"10.2147\/JBM.S232644","article-title":"Understanding sideroblastic anemia: an overview of genetics, epidemiology, pathophysiology and current therapeutic options","volume":"11","author":"Abu-Zeinah","year":"2020","journal-title":"J. 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