{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T03:15:35Z","timestamp":1777518935782,"version":"3.51.4"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2020,1,21]],"date-time":"2020-01-21T00:00:00Z","timestamp":1579564800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Broad Institute - Israel\u00a0Science Foundation partnership","award":["2435\/16"],"award-info":[{"award-number":["2435\/16"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>Differential network analysis, designed to highlight network changes between conditions, is an important paradigm in network biology. However, differential network analysis methods have been typically designed to compare between two conditions and were rarely applied to multiple protein interaction networks (interactomes). Importantly, large-scale benchmarks for their evaluation have been lacking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Here, we present a framework for assessing the ability of differential network analysis of multiple human tissue interactomes to highlight tissue-selective processes and disorders. For this, we created a benchmark of 6499 curated tissue-specific Gene Ontology biological processes. We applied five methods, including four differential network analysis methods, to construct weighted interactomes for 34 tissues. Rigorous assessment of this benchmark revealed that differential analysis methods perform well in revealing tissue-selective processes (AUCs of 0.82\u20130.9). Next, we applied differential network analysis to illuminate the genes underlying tissue-selective hereditary disorders. For this, we curated a dataset of 1305 tissue-specific hereditary disorders and their manifesting tissues. Focusing on subnetworks containing the top 1% differential interactions in disease-relevant tissue interactomes revealed significant enrichment for disorder-causing genes in 18.6% of the cases, with a significantly high success rate for blood, nerve, muscle and heart diseases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Summary<\/jats:title>\n                    <jats:p>Altogether, we offer a framework that includes expansive manually curated datasets of tissue-selective processes and disorders to be used as benchmarks or to illuminate tissue-selective processes and genes. Our results demonstrate that differential analysis of multiple human tissue interactomes is a powerful tool for highlighting processes and genes with tissue-selective functionality and clinical impact.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>Datasets are available as part of the Supplementary data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Supplementary information<\/jats:title>\n                    <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btaa034","type":"journal-article","created":{"date-parts":[[2020,1,16]],"date-time":"2020-01-16T08:50:12Z","timestamp":1579164612000},"page":"2821-2828","source":"Crossref","is-referenced-by-count":34,"title":["Differential network analysis of multiple human tissue interactomes highlights tissue-selective processes and genetic disorder genes"],"prefix":"10.1093","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5764-1066","authenticated-orcid":false,"given":"Omer","family":"Basha","sequence":"first","affiliation":[{"name":"Department of Clinical Biochemistry and Pharmacology , Faculty of Health Sciences"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chanan M","family":"Argov","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry and Pharmacology , Faculty of Health Sciences"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raviv","family":"Artzy","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry and Pharmacology , Faculty of Health Sciences"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yazeed","family":"Zoabi","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry and Pharmacology , Faculty of Health Sciences"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Idan","family":"Hekselman","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry and Pharmacology , Faculty of Health Sciences"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liad","family":"Alfandari","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry and Pharmacology , Faculty of Health Sciences"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vered","family":"Chalifa-Caspi","sequence":"additional","affiliation":[{"name":"National Institute for Biotechnology in the Negev , Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8279-7898","authenticated-orcid":false,"given":"Esti","family":"Yeger-Lotem","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry and Pharmacology , Faculty of Health Sciences"},{"name":"National Institute for Biotechnology in the Negev , Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,1,21]]},"reference":[{"key":"2023013111491211600_btaa034-B1","doi-asserted-by":"crossref","first-page":"D789","DOI":"10.1093\/nar\/gku1205","article-title":"OMIM.org: online Mendelian Inheritance in Man (OMIM), an online catalog of human genes and genetic disorders","volume":"43","author":"Amberger","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"2023013111491211600_btaa034-B2","doi-asserted-by":"crossref","first-page":"D525","DOI":"10.1093\/nar\/gkp878","article-title":"The IntAct molecular interaction database in 2010","volume":"38","author":"Aranda","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"2023013111491211600_btaa034-B3","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1126\/science.1195618","article-title":"Rewiring of genetic networks in response to DNA damage","volume":"330","author":"Bandyopadhyay","year":"2010","journal-title":"Science"},{"key":"2023013111491211600_btaa034-B4","doi-asserted-by":"crossref","first-page":"e1003632","DOI":"10.1371\/journal.pcbi.1003632","article-title":"Comparative analysis of human tissue interactomes reveals factors leading to tissue-specific manifestation of hereditary diseases","volume":"10","author":"Barshir","year":"2014","journal-title":"PLoS Comput. 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