{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T14:42:42Z","timestamp":1787928162057,"version":"build-2784847793"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012063","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T00:00:00Z","timestamp":1710979200000}}],"reference-count":60,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2024,3,11]],"date-time":"2024-03-11T00:00:00Z","timestamp":1710115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["R03DA039745, R01DA047063, R01DA047820, R01DA038632"],"award-info":[{"award-number":["R03DA039745, R01DA047063, R01DA047820, R01DA038632"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["U01-AA020790"],"award-info":[{"award-number":["U01-AA020790"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["U10 AA013566"],"award-info":[{"award-number":["U10 AA013566"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIAA","award":["U24 AA020794"],"award-info":[{"award-number":["U24 AA020794"]}]},{"DOI":"10.13039\/100000027","name":"NIAAA","doi-asserted-by":"crossref","award":["U24-AA020794, U01-AA020795, U01-AA020799; U10-AA013566"],"award-info":[{"award-number":["U24-AA020794, U01-AA020795, U01-AA020799; U10-AA013566"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["R01-DA035616"],"award-info":[{"award-number":["R01-DA035616"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008374","name":"Emory CFAR","doi-asserted-by":"crossref","award":["P30-AI-050409"],"award-info":[{"award-number":["P30-AI-050409"]}],"id":[{"id":"10.13039\/100008374","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Epigenome-wide association studies (EWAS) have identified CpG sites associated with HIV infection in blood cells in bulk, which offer limited knowledge of cell-type specific methylation patterns associated with HIV infection. In this study, we aim to identify differentially methylated CpG sites for HIV infection in immune cell types: CD4+ T-cells, CD8+ T-cells, B cells, Natural Killer (NK) cells, and monocytes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Applying a computational deconvolution method, we performed a cell-type based EWAS for HIV infection in three independent cohorts (N\n                      <jats:sub>total<\/jats:sub>\n                      = 1,382). DNA methylation in blood or in peripheral blood mononuclear cells (PBMCs) was profiled by an array-based method and then deconvoluted by Tensor Composition Analysis (TCA). The TCA-computed CpG methylation in each cell type was first benchmarked by bisulfite DNA methylation capture sequencing in a subset of the samples. Cell-type EWAS of HIV infection was performed in each cohort separately and a meta-EWAS was conducted followed by gene set enrichment analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The meta-analysis unveiled a total of 2,021 cell-type unique significant CpG sites for five inferred cell types. Among these inferred cell-type unique CpG sites, the concordance rate in the three cohorts ranged from 96% to 100% in each cell type. Cell-type level meta-EWAS unveiled distinct patterns of HIV-associated differential CpG methylation, where 74% of CpG sites were unique to individual cell types (false discovery rate, FDR &lt;0.05). CD4+ T-cells had the largest number of unique HIV-associated CpG sites (N = 1,624) compared to any other cell type. Genes harboring significant CpG sites are involved in immunity and HIV pathogenesis (e.g. CD4+ T-cells:\n                      <jats:italic>NLRC5<\/jats:italic>\n                      ,\n                      <jats:italic>CX3CR1<\/jats:italic>\n                      , B cells:\n                      <jats:italic>IFI44L<\/jats:italic>\n                      , NK cells:\n                      <jats:italic>IL12R<\/jats:italic>\n                      , monocytes:\n                      <jats:italic>IRF7<\/jats:italic>\n                      ), and in oncogenesis (e.g. CD4+ T-cells:\n                      <jats:italic>BCL family<\/jats:italic>\n                      ,\n                      <jats:italic>PRDM16<\/jats:italic>\n                      , monocytes:\n                      <jats:italic>PRDM16<\/jats:italic>\n                      ,\n                      <jats:italic>PDCD1LG2<\/jats:italic>\n                      ). HIV-associated CpG sites were enriched among genes involved in HIV pathogenesis and oncogenesis that were enriched among interferon-\u03b1 and -\u03b3, TNF-\u03b1, inflammatory response, and apoptotic pathways.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings uncovered computationally inferred cell-type specific modifications in the host epigenome for people with HIV that contribute to the growing body of evidence regarding HIV pathogenesis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.ppat.1012063","type":"journal-article","created":{"date-parts":[[2024,3,11]],"date-time":"2024-03-11T13:43:27Z","timestamp":1710164607000},"page":"e1012063","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Computationally inferred cell-type specific epigenome-wide DNA methylation analysis unveils distinct methylation patterns among immune cells for HIV infection in three cohorts"],"prefix":"10.1371","volume":"20","author":[{"given":"Xinyu","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ral E.","family":"Vandenhoudt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunhua","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent C.","family":"Marconi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mardge H.","family":"Cohen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuoheng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy C.","family":"Justice","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley E.","family":"Aouizerat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6472-7052","authenticated-orcid":true,"given":"Ke","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,3,11]]},"reference":[{"issue":"6","key":"ppat.1012063.ref001","doi-asserted-by":"crossref","first-page":"e207954","DOI":"10.1001\/jamanetworkopen.2020.7954","article-title":"Comparison of Overall and Comorbidity-Free Life Expectancy 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