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CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells\u2019 metabolism is dysregulated in these pathologies and represents an opportunity for drug discovery and development. Genome-scale metabolic modeling offers an opportunity to accelerate drug discovery by providing high-quality information about possible target space in the context of a modeled disease. Here, we develop genome-scale models of na\u00efve, Th1, Th2, and Th17 CD4\n                    <jats:sup>+<\/jats:sup>\n                    T-cell subtypes to map metabolic perturbations in rheumatoid arthritis, multiple sclerosis, and primary biliary cholangitis. We subjected these models to in silico simulations for drug response analysis of existing FDA-approved drugs and compounds. Integration of disease-specific differentially expressed genes with altered reactions in response to metabolic perturbations identified 68 drug targets for the three autoimmune diseases. In vitro experimental validation, together with literature-based evidence, showed that modulation of fifty percent of identified drug targets suppressed CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells, further increasing their potential impact as therapeutic interventions. Our approach can be generalized in the context of other diseases, and the metabolic models can be further used to dissect CD4\n                    <jats:sup>+<\/jats:sup>\n                    T-cell metabolism.\n                  <\/jats:p>","DOI":"10.1038\/s41540-020-00165-3","type":"journal-article","created":{"date-parts":[[2021,1,22]],"date-time":"2021-01-22T06:40:00Z","timestamp":1611297600000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Integrative computational approach identifies drug targets in CD4+ T-cell-mediated immune disorders"],"prefix":"10.1038","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7528-3568","authenticated-orcid":false,"given":"Bhanwar Lal","family":"Puniya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rada","family":"Amin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bailee","family":"Lichter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Moore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Ciurej","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sydney J.","family":"Bennett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ab Rauf","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5640-7422","authenticated-orcid":false,"given":"Matteo","family":"Barberis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3653-1906","authenticated-orcid":false,"given":"Tom\u00e1\u0161","family":"Helikar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,22]]},"reference":[{"key":"165_CR1","doi-asserted-by":"publisher","first-page":"1557","DOI":"10.1182\/blood-2008-05-078154","volume":"112","author":"J Zhu","year":"2008","unstructured":"Zhu, J. & Paul, W. 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