{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T11:25:25Z","timestamp":1787570725095,"version":"build-2736575974"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"Supplement_2","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":23,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["2266\/25"],"award-info":[{"award-number":["2266\/25"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U19AG057377"],"award-info":[{"award-number":["U19AG057377"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Raymond and Beverly Sackler Chair in Bioinformatics at Tel Aviv University"},{"name":"Safra Center for Bioinformatics at Tel-Aviv University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>A central goal in human gut microbiome research is to identify disease-associated functional shifts, an objective increasingly pursued through metagenomic and metabolomic assays. However, common differential abundance analyses of genes or metabolites often yield long and difficult-to-interpret feature lists. Aggregating features into predefined pathways can improve interpretability but relies on fixed pathway boundaries that may not reflect context-specific functional changes. Moreover, even when paired metagenomic-metabolomic data are available, they are often analyzed separately or linked only through simple statistical associations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We introduce MAAMOUL, a knowledge-based computational framework that integrates metagenomic and metabolomic data to identify disease-associated, data-driven microbial metabolic modules. Leveraging prior knowledge of bacterial metabolism, MAAMOUL maps disease-association scores onto a global microbiome-wide metabolic network and identifies custom modules enriched for altered genes and metabolites. Applying MAAMOUL to inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) datasets revealed significant disease-associated modules not detected by conventional pathway-level analysis. In IBD, modules reflected disrupted sulfur and aromatic amino acid metabolism and enhanced microbial nucleotide salvage, whereas in IBS they linked purine and nicotinate\/nicotinamide metabolism. These results demonstrate that network-guided multi-omic integration can uncover coherent functional shifts in the gut microbiome overlooked by single-omic or purely statistical approaches.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>MAAMOUL is available as an R package at https:\/\/github.com\/borenstein-lab\/MAAMOUL.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btag467","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T13:19:49Z","timestamp":1783084789000},"source":"Crossref","is-referenced-by-count":0,"title":["MAAMOUL: metabolic network-based discovery of microbiome-metabolome shifts in disease"],"prefix":"10.1093","volume":"42","author":[{"given":"Efrat","family":"Muller","sequence":"first","affiliation":[{"name":"Blavatnik School of Computer Science and AI, Tel Aviv University , Tel Aviv, 6997801,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8032-8595","authenticated-orcid":false,"given":"Shiri","family":"Baum","sequence":"additional","affiliation":[{"name":"Blavatnik School of Computer Science and AI, Tel Aviv University , Tel Aviv, 6997801,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3002-0945","authenticated-orcid":false,"given":"Elhanan","family":"Borenstein","sequence":"additional","affiliation":[{"name":"Blavatnik School of Computer Science and AI, Tel Aviv University , Tel Aviv, 6997801,","place":["Israel"]},{"name":"Gray Faculty of Medical & Health Sciences, Tel Aviv University , Tel Aviv, 6997801,","place":["Israel"]},{"name":"Santa Fe Institute , Santa Fe, NM 87501,","place":["United 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