{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:02:21Z","timestamp":1785402141010,"version":"3.56.0"},"posted":{"date-parts":[[2025,10,9]]},"group-title":"Systems Biology","reference-count":25,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:00:00Z","timestamp":1759968000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["R01 DK130294"],"award-info":[{"award-number":["R01 DK130294"]}],"id":[{"id":"https:\/\/ror.org\/00adh9b73","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01 AA028436"],"award-info":[{"award-number":["R01 AA028436"]}],"id":[{"id":"https:\/\/ror.org\/02jzrsm59","id-type":"ROR","asserted-by":"publisher"}]},{"name":"NIDDK that funds the Pittsburgh Liver Research Center","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":[],"accepted":{"date-parts":[[2025,10,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Next generation sequencing can identify novel gene expression patterns in disease. Beyond differentially expressed genes analysis, we investigated the ability of within-population diversity (\u03b1-diversity) of the transcriptome to reveal new biological information in alcohol-related liver disease (ALD), comparing Differential Shannon diversity (DSD) to transcriptome heterogeneity changes. RNA sequencing data from normal livers and patients with early silent ALD and severe AH were analyzed. \u03b1-diversity indices and Percent 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 differentially expressed genes (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 novel genes and pathways not highlighted by DEG. Importantly, DSD more effectively identified differences between preclinical ALD and AH severity stages. ALD decreases hepatic transcriptome heterogeneity, favoring pathways associated with organ damage or damage response. Preclinical and clinical ALD led to differential heterogeneity patterns that may provide new disease insights. DSD analysis identified enriched pathways missed by standard DEG analyses, potentially yielding novel insight into disease mechanisms and biomarkers.<\/jats:p>\n                <jats:sec>\n                  <jats:title>Graphical abstract<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" orientation=\"portrait\" fig-type=\"figure\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"681263v1_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>","DOI":"10.1101\/2025.10.08.681263","type":"posted-content","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T04:35:13Z","timestamp":1760070913000},"source":"Crossref","is-referenced-by-count":0,"title":["Alpha diversity analysis of hepatic transcriptome reveals novel pathways in alcohol-related hepatitis"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0150-6308","authenticated-orcid":false,"given":"Sudrishti","family":"Chaudhary","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Jun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marissa","family":"Di","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5395-5682","authenticated-orcid":false,"given":"Juliane I","family":"Beier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramon","family":"Bataller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josepmaria","family":"Argemi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3172-3132","authenticated-orcid":false,"given":"Panayiotis V","family":"Benos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin E","family":"Arteel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025101403400582000_2025.10.08.681263v1.1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.04.044"},{"key":"2025101403400582000_2025.10.08.681263v1.2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2018.05.011"},{"key":"2025101403400582000_2025.10.08.681263v1.3","doi-asserted-by":"crossref","unstructured":"Satam H , Joshi K , Mangrolia U , Waghoo S , Zaidi G , Rawool S , et al. 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