{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T18:03:29Z","timestamp":1780077809232,"version":"3.54.0"},"reference-count":54,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2019s Horizon 2020","award":["EJP RD COFUND-EJP N\u00b0 825575"],"award-info":[{"award-number":["EJP RD COFUND-EJP N\u00b0 825575"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Porto-sinusoidal vascular disease (PSVD) is a complex, rare liver disease characterized by the absence of cirrhosis, with or without the presence of portal hypertension or histological lesions. Given the knowledge gaps in the mechanisms involved in this disease with unknown etiology, we used omics-based approaches to further elucidate the pathways affected by PSVD, facilitating improvements in the prognosis, diagnosis, and treatment options for these patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We applied gene set enrichment analysis (GSEA) and weighted gene coexpression network analysis (WGCNA) to identify pathways dysregulated in PSVD. Network construction and visualization were performed in Cytoscape to explore interconnectivity among enriched processes. Within key modules, candidate genes were prioritized by ranking approaches and cross-referenced with findings from previous studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results and conclusion<\/jats:title>\n                    <jats:p>In this study using both module eigengene correlation network analysis and GSEA, a novel coordinated dysregulation in PSVD was identified characterized by the simultaneous activation of immune and signaling pathways alongside the suppression of metabolic, ribosomal, and mitochondrial programs, highlighting a critical antagonistic interplay between these systems. Alterations in ribosomal proteins, ATP synthase subunits, and serpin family members highlight translational, bioenergetic, and anticoagulant dysfunction as core mechanisms. Together, these findings define PSVD as a disorder of integrated immune, vascular, and metabolic imbalance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0347338","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T17:30:37Z","timestamp":1780075837000},"page":"e0347338","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["GSEA and the coexpression network approach identify novel pathway connections of molecular processes affected in Porto-sinusoidal vascular disease"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2878-4049","authenticated-orcid":true,"given":"Aishwarya","family":"Iyer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0613-3651","authenticated-orcid":true,"given":"Cenna","family":"Doornbos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Evelo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Kutmon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7770-620X","authenticated-orcid":true,"given":"Friederike","family":"Ehrhart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"issue":"5","key":"pone.0347338.ref001","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/S2468-1253(19)30047-0","article-title":"Porto-sinusoidal vascular disease: proposal and description of a novel entity","volume":"4","author":"A De Gottardi","year":"2019","journal-title":"Lancet Gastroenterol Hepatol"},{"issue":"7","key":"pone.0347338.ref002","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1111\/liv.12972","article-title":"Metabolomics as a diagnostic tool for idiopathic non-cirrhotic portal hypertension","volume":"36","author":"S Seijo","year":"2016","journal-title":"Liver Int"},{"issue":"4","key":"pone.0347338.ref003","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1016\/j.jhep.2021.05.014","article-title":"Co-expression gene network analysis reveals novel regulatory pathways involved in porto-sinusoidal vascular disease","volume":"75","author":"V Hern\u00e1ndez-Gea","year":"2021","journal-title":"J Hepatol"},{"issue":"1","key":"pone.0347338.ref004","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1111\/gbb.12106","article-title":"Beyond modules and hubs: the potential of gene coexpression networks for investigating molecular mechanisms of complex brain disorders","volume":"13","author":"C Gaiteri","year":"2014","journal-title":"Genes Brain Behav"},{"issue":"8","key":"pone.0347338.ref005","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/cgt.2017.23","article-title":"Identification of breast cancer mechanism based on weighted gene coexpression network analysis","volume":"24","author":"X Guo","year":"2017","journal-title":"Cancer Gene Ther"},{"issue":"13","key":"pone.0347338.ref006","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1093\/bioinformatics\/btn224","article-title":"lumi: a pipeline for processing Illumina microarray","volume":"24","author":"P Du","year":"2008","journal-title":"Bioinformatics"},{"issue":"7","key":"pone.0347338.ref007","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"ME Ritchie","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"pone.0347338.ref008","volume-title":"R: a language and environment for statistical computing","author":"R Core Team","year":"2025"},{"issue":"5","key":"pone.0347338.ref009","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: an R package for comparing biological themes among gene clusters","volume":"16","author":"G Yu","year":"2012","journal-title":"OMICS"},{"issue":"43","key":"pone.0347338.ref010","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"A Subramanian","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0347338.ref011","doi-asserted-by":"crossref","unstructured":"Korotkevich G, Sukhov V, Budin N, Shpak B, Artyomov MN, Sergushichev A. 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