{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T15:07:57Z","timestamp":1773155277834,"version":"3.50.1"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2025,6,28]],"date-time":"2025-06-28T00:00:00Z","timestamp":1751068800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007431","name":"NRF","doi-asserted-by":"publisher","award":["RS-2023-00276559"],"award-info":[{"award-number":["RS-2023-00276559"]}],"id":[{"id":"10.13039\/100007431","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"AMED","doi-asserted-by":"publisher","award":["23tk0124003h0001"],"award-info":[{"award-number":["23tk0124003h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"AMED","doi-asserted-by":"publisher","award":["24tk0124003h0002"],"award-info":[{"award-number":["24tk0124003h0002"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"name":"JSPS KAKENHI","award":["JP24H00009"],"award-info":[{"award-number":["JP24H00009"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Gene network analysis is essential for understanding the complex mechanisms underlying diseases, which often involve disruptions in molecular networks rather than individual genes. Despite the availability of large-scale omics datasets and computational tools for gene network analysis, interpretation of the biological relevance of these extensive networks remains challenging.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We propose a novel computational strategy, gene behaviors-based network enrichment analysis, which systematically identifies functional pathways enriched in phenotype-specific gene networks. Our novel method incorporates comprehensive network characteristics, i.e. gene expression levels, edge strengths, and structural patterns of edges, to rank genes based on activity and assess pathway enrichment, effectively identifying functional pathways enriched within these networks. Through simulation studies, our strategy demonstrated superior performance compared with that of existing methods in identifying enriched pathways. We applied this strategy to whole-blood RNA-seq data from 1102 COVID-19 samples provided by the Japan COVID-19 Task Force. The analysis revealed immune disease pathways enriched with COVID-19 severity-specific gene networks, including \u201cSystemic lupus erythematosus\u201d in asymptomatic and severe samples and \u201cInflammatory bowel disease,\u201d \u201cPrimary immunodeficiency,\u201d and \u201cRheumatoid arthritis\u201d in mild samples. Key biomarkers of COVID-19, such as CXCL8, S100A9, and HLA class I genes, have been identified as critical hub genes and the main players within these networks.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>Code is available in Figshare (https:\/\/doi.org\/10.6084\/m9.figshare.29093648.v3).<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btaf378","type":"journal-article","created":{"date-parts":[[2025,6,28]],"date-time":"2025-06-28T12:20:00Z","timestamp":1751113200000},"source":"Crossref","is-referenced-by-count":2,"title":["Gene behaviors-based network enrichment analysis and its application to reveal immune disease pathways enriched with COVID-19 severity-specific gene networks"],"prefix":"10.1093","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2773-8596","authenticated-orcid":false,"given":"Heewon","family":"Park","sequence":"first","affiliation":[{"name":"School of Mathematics, Statistics and Data Science, Sungshin Women\u2019s University , Seoul,","place":["Korea"]},{"name":"Data Science Center, Sungshin Women\u2019s University, Seoul,","place":["Korea"]},{"name":"M&D Data Science Center, Institute of Integrated Research, Institute of Science Tokyo , Tokyo,","place":["Japan"]},{"name":"Human Genome Center, Institute of Medical Science, University of Tokyo , Tokyo,","place":["Japan"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2989-308X","authenticated-orcid":false,"given":"Seiya","family":"Imoto","sequence":"additional","affiliation":[{"name":"Human Genome Center, Institute of Medical Science, University of Tokyo , Tokyo,","place":["Japan"]}]},{"given":"Satory","family":"Miyano","sequence":"additional","affiliation":[{"name":"M&D Data Science Center, Institute of Integrated Research, Institute of Science Tokyo , Tokyo,","place":["Japan"]},{"name":"Human Genome Center, Institute of Medical Science, University of Tokyo , Tokyo,","place":["Japan"]}]}],"member":"286","published-online":{"date-parts":[[2025,6,28]]},"reference":[{"key":"2025072715114122400_btaf378-B1","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: a practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J R Stat Soc Ser B"},{"key":"2025072715114122400_btaf378-B2","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/s41423-023-00974-6","article-title":"The chemokines CXCL8 and CXCL12: molecular and functional properties, role in disease and efforts towards pharmacological intervention","volume":"20","author":"Cambier","year":"2023","journal-title":"Cell Mol 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