{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T20:12:57Z","timestamp":1778875977209,"version":"3.51.4"},"reference-count":33,"publisher":"American Society for Clinical Investigation","issue":"5","license":[{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"vor","delay-in-days":60,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH grant awarded by the National Institute of Diabetes and Digestive and Kidney Diseases","award":["R01 DK130294"],"award-info":[{"award-number":["R01 DK130294"]}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse & Alcoholism","doi-asserted-by":"crossref","award":["R01 AA028436"],"award-info":[{"award-number":["R01 AA028436"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Center Core Grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) that funds the Pittsburgh Liver Research Center (PLRC) at the University of Pittsburgh.","award":["P30 DK120531"],"award-info":[{"award-number":["P30 DK120531"]}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"crossref","award":["R01 HL159805)"],"award-info":[{"award-number":["R01 HL159805)"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,9]]},"abstract":"<jats:p>Next-generation sequencing can identify previously uncharacterized gene expression patterns in disease. Beyond differentially expressed gene (DEG) analysis, we investigated the ability of within-population diversity (\u03b1-diversity) of the transcriptome to reveal additional biological information in alcohol-associated liver disease (ALD), comparing differential Shannon diversity (DSD) to transcriptome heterogeneity changes. RNA sequencing data from normal livers and patients with early ALD and severe AH were analyzed. \u03b1-Diversity indices and percentage Shannon diversity of a gene, which refers to this gene\u2019s contribution to total Shannon entropy, were calculated. Ingenuity pathway analysis identified canonical pathways determined by DEG and DSD approaches. ALD significantly decreased hepatic transcriptome \u03b1-diversity, correlating with increased relative contribution of select genes. These changes were driven by lower-abundance gene expression loss. DEG and DSD analyses showed overlapping genes and canonical pathways, but DSD also identified additional genes and pathways not highlighted by DEGs, including fatty acid oxidation, extracellular matrix degradation, and cholesterol metabolism pathways that may represent additional therapeutic targets. Importantly, DSD more effectively identified differences between ASH and AH. Overall, \u03b1-diversity analysis revealed that ALD progressively reduces transcriptome heterogeneity, and that DSD provides complementary insights into disease mechanisms missed by standard approaches.<\/jats:p>","DOI":"10.1172\/jci.insight.200727","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T17:00:56Z","timestamp":1767891656000},"source":"Crossref","is-referenced-by-count":0,"title":["\u03b1-Diversity analysis of hepatic transcriptome reveals distinct pathways in alcohol-associated hepatitis"],"prefix":"10.1172","volume":"11","author":[{"given":"Sudrishti","family":"Chaudhary","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia-Jun","family":"Liu","sequence":"additional","affiliation":[{"name":"Pharmacology and Chemical Biology,"},{"name":"Organ Pathobiology and Therapeutics Institute,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Liu","sequence":"additional","affiliation":[{"name":"Pharmacology and Chemical Biology,"},{"name":"Organ Pathobiology and Therapeutics Institute,"},{"name":"Pittsburgh Liver Research Center, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marissa","family":"Di","sequence":"additional","affiliation":[{"name":"Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliane I.","family":"Beier","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition,"},{"name":"Pittsburgh Liver Research Center, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1119-7799","authenticated-orcid":true,"given":"Ramon","family":"Bataller","sequence":"additional","affiliation":[{"name":"Institut d\u2019Investigacions Biomediques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josepmaria","family":"Argemi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition,"},{"name":"Department of Internal Medicine, Liver Unit, Clinical University of Navarra, Navarra, Spain."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3172-3132","authenticated-orcid":true,"given":"Panayiotis V.","family":"Benos","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University of Florida, Gainesville, Florida, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gavin E.","family":"Arteel","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition,"},{"name":"Pittsburgh Liver Research Center, and"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"232","published-online":{"date-parts":[[2026,1,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.04.044"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2018.05.011"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.conctc.2023.101074"},{"issue":"7","key":"B4","article-title":"Next-generation sequencing technology: current trends and advancements","volume":"12","author":"Satam","year":"2023","journal-title":"Biology (Basel)"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2022.08.009"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-020-06461-6"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt703"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/nbt0410-322"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11004-3"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06318-7"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24054344"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1002\/hep4.1793"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1172\/JCI157780"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.05.017"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26419"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31680"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12150"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1007\/s10238-023-01121-1"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2022.09.010"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3389\/fpls.2022.839407"},{"key":"B21","first-page":"178","article-title":"Evolution of diversity in plant communities","volume":"22","author":"Whittaker","year":"1969","journal-title":"Brookhaven Symp Biol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1126\/science.147.3655.250"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6941.2003.tb01040.x"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1521291113"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1111\/mec.13536"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0030126"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0609333103"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2024.148599"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1009939"},{"issue":"1828","key":"B30","article-title":"Rare species contribute disproportionately to the functional structure of species assemblages","volume":"283","author":"Leit\u00e3o","year":"2016","journal-title":"Proc Biol Sci"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1002\/ece3.915"},{"issue":"1600","key":"B32","first-page":"2501","article-title":"Negative environmental perturbations may improve species persistence","volume":"273","author":"Robert","year":"2006","journal-title":"Proc Biol Sci"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0110501"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/200727\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T19:29:15Z","timestamp":1778873355000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/200727"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,8]]},"references-count":33,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,1,27]]},"published-print":{"date-parts":[[2026,3,9]]}},"alternative-id":["10.1172\/jci.insight.200727"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.200727","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,8]]},"article-number":"e200727"}}