{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T23:20:26Z","timestamp":1793834426063,"version":"4.6.1"},"reference-count":81,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010767","name":"Innovative Medicines Initiative","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010767","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Ulcerative colitis (UC) is an idiopathic chronic inflammatory disease of the colon characterized by severe disease burden and multiple co-morbidities. Currently, the endoscopic Mayo score is considered the gold standard for assessing disease severity in UC. However, the molecular mechanisms underlying severity are still poorly understood. This study aimed to better understand the molecular alterations associated with severity in UC. To achieve this goal, gene expression and DNA methylation were measured in paired blood and colonic tissue samples from UC patients at different severity stages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Differential gene expression and methyl-ation analyses, as well as integrative multi-omics network analysis including both omics layers and tissues were performed. A hybrid framework combining prior knowledge and text-mining was deployed to contextualize the associations retrieved from the multi-omics network.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our analyses suggested that mild UC was associated with molecular alterations affecting mainly the colon, while severe UC had systemic consequences. Moreover, the combination of the differentially expressed genes and methylated regions found in blood and colonic tissue allowed us to suggest potential associations between them and formulate hypothesis on novel mechanisms associated with different UC severity stages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Among them, fibrogenesis, colonic epithelial cell death, and Tuft cell-related processes seemed to be associated with milder disease stages. In contrast, neutrophil-driven innate immune response and complex B cell and CD4 T cell interactions were suggested as potential mechanisms involved in severe UC. Finally, the findings of this study led to the formulation of a hypothesis suggesting that impaired PPARG anti-inflammatory regulation associated with colonic LCN2 activity might play a relevant role in UC severity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1884480","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T05:36:00Z","timestamp":1784612160000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["From tissue to blood: an integrated multi-omics signature identifies fibrogenesis and neutrophil activation as key drivers of ulcerative colitis severity"],"prefix":"10.3389","volume":"17","author":[{"given":"E.","family":"Ozcariz","sequence":"first","affiliation":[{"name":"Center for Health and Bioresources, Molecular Diagnostics, AIT Austrian Institute of Technology GmbH","place":["Giefinggasse, Vienna, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Ostaszewski","sequence":"additional","affiliation":[{"name":"Bioinformatics Core Unit, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg","place":["Esch-sur-Alzette, Luxembourg"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O.","family":"Lopata","sequence":"additional","affiliation":[{"name":"Bioinformatics Core Unit, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg","place":["Esch-sur-Alzette, Luxembourg"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Ciglar","sequence":"additional","affiliation":[{"name":"Center for Health and Bioresources, Molecular Diagnostics, AIT Austrian Institute of Technology GmbH","place":["Giefinggasse, Vienna, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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F.","family":"Li Yim","sequence":"additional","affiliation":[{"name":"Tytgat Institute for Liver and Intestinal Research, Amsterdam UMC, Location University of Amsterdam","place":["Amsterdam, Netherlands"]},{"name":"Amsterdam Gastroenterology Endocrinology Metabolism (AGEM)","place":["Amsterdam, Netherlands"]},{"name":"Department of Gastroenterology and Hepatology, Amsterdam UMC, Location University of Amsterdam","place":["Amsterdam, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Pruijt","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Amsterdam UMC, Location University of Amsterdam","place":["Amsterdam, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X.","family":"Wang","sequence":"additional","affiliation":[{"name":"Bioinformatics Core Unit, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg","place":["Esch-sur-Alzette, Luxembourg"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. 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Oppenheimer Center for Neurobiology of Stress and Resilience, UCLA","place":["Los Angeles, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Tran","sequence":"additional","affiliation":[{"name":"Institute of Clinical Molecular Biology, University of Kiel and University Hospital Schleswig-Holstein","place":["Kiel, Germany"]},{"name":"Department Internal Medicine I, Kiel University, University Hospital Schleswig Holstein","place":["Kiel, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Satagopam","sequence":"additional","affiliation":[{"name":"Bioinformatics Core Unit, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg","place":["Esch-sur-Alzette, Luxembourg"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. 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