{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T22:13:44Z","timestamp":1794262424010,"version":"4.9.0"},"reference-count":49,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T00:00:00Z","timestamp":1661299200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T00:00:00Z","timestamp":1661299200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Institutional Research and Academic Career Development Award","award":["K12GM068524"],"award-info":[{"award-number":["K12GM068524"]}],"id":[{"id":"https:\/\/ror.org\/02xjhr934","id-type":"ROR","asserted-by":"crossref"}]},{"name":"UCSD Gastroenterology T32 training grant","award":["DK 0070202"],"award-info":[{"award-number":["DK 0070202"]}]},{"name":"UCSD Gastroenterology T32 training grant","award":["DK 0070202"],"award-info":[{"award-number":["DK 0070202"]}]},{"name":"American Gastroenterology Association Research Scholar Award"},{"name":"Crohn\u2019s and Colitis Foundation through a Litwin IBD Pioneers Program Grant","id":[{"id":"https:\/\/ror.org\/05f2xbq60","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Collaborative Center for Multiplexed Proteomics"},{"name":"San Diego Digestive Disease Center","award":["P30 DK120515"],"award-info":[{"award-number":["P30 DK120515"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Microbiome"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Crohn\u2019s disease (CD), an inflammatory bowel disease (IBD) subtype, results from pathologic interactions between host cells and its resident gut microbes. CD manifests in both isolated disease locations (ileum or colon) or a combination of locations (ileocolonic). To date, a comprehensive understanding of how isolated CD subtypes influence molecular profiles remains outstanding. To address this, we sought to define CD location signatures by leveraging a large cross-sectional feature set captured from the stool of over 200 IBD patients and healthy controls using metaproteomics, shotgun metagenomics, 16S rRNA sequencing, metabolomic profiling, and host genetics paired with clinical endoscopic assessments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Neither metagenomic nor host genetics alone distinguished CD location subtypes. In contrast, ileal and colonic CD were distinguished using mass spectrometry-based methods (metabolomics or metaproteomics) or a combined multi-omic feature set. This multi-omic feature set revealed colonic CD was strongly associated with neutrophil-related proteins. Additionally, colonic CD displayed a disease-severity-related association with\n                      <jats:italic>Bacteroides vulgatus<\/jats:italic>\n                      . Colonic CD and ulcerative colitis profiles harbored strikingly similar feature enrichments compared to ileal CD, including neutrophil-related protein enrichments. Compared to colonic CD, ileal CD profiles displayed increased primary and secondary bile acid levels and concomitant shifts in taxa with noted sensitivities such as\n                      <jats:italic>Faecalibacterium prausnitzii<\/jats:italic>\n                      or affinities for bile acid-rich environments, including\n                      <jats:italic>Gammaproteobacteria<\/jats:italic>\n                      and\n                      <jats:italic>Blautia<\/jats:italic>\n                      sp. Having shown robust molecular and microbial distinctions tied to CD locations, we leveraged these profiles to generate location-specific disease severity biomarkers that surpass the performance of Calprotectin.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      When compared using multi-omics features, colonic- and ileal-isolated CD subtypes display striking differences that suggest separate location-specific pathologies. Colonic CD\u2019s strong similarity to ulcerative colitis, including neutrophil and\n                      <jats:italic>Bacteroides vulgatus<\/jats:italic>\n                      involvement, is also evidence of a shared pathology for colonic-isolated IBD subtypes, while ileal CD maintains a unique, bile acid-driven profile. More broadly, this study demonstrates the power of multi-omics approaches for IBD biomarker discovery and elucidating the underlying biology.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40168-022-01331-x","type":"journal-article","created":{"date-parts":[[2022,8,23]],"date-time":"2022-08-23T21:02:27Z","timestamp":1661288547000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":82,"title":["Location-specific signatures of Crohn\u2019s disease at a multi-omics scale"],"prefix":"10.1186","volume":"10","author":[{"given":"Carlos G.","family":"Gonzalez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert H.","family":"Mills","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiyun","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Consuelo","family":"Sauceda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rob","family":"Knight","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parambir S.","family":"Dulai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Gonzalez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,8,24]]},"reference":[{"key":"1331_CR1","doi-asserted-by":"publisher","first-page":"2634","DOI":"10.1016\/j.cgh.2019.04.040","volume":"17","author":"PS Dulai","year":"2019","unstructured":"Dulai PS, et al. Should we divide Crohn\u2019s disease into ileum-dominant and isolated colonic diseases? Clin Gastroenterol Hepatol. 2019;17:2634\u201343.","journal-title":"Clin Gastroenterol Hepatol"},{"key":"1331_CR2","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1111\/apt.14852","volume":"48","author":"S Singh","year":"2018","unstructured":"Singh S, Fumery M, Sandborn WJ, Murad MH. Systematic review and network meta-analysis: first- and second-line biologic therapies for moderate-severe Crohn\u2019s disease. Aliment Pharmacol Ther. 2018;48:394\u2013409.","journal-title":"Aliment Pharmacol Ther"},{"key":"1331_CR3","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1136\/gutjnl-2016-312673","volume":"66","author":"S Subramanian","year":"2017","unstructured":"Subramanian S, Ekbom A, Rhodes JM. Recent advances in clinical practice: a systematic review of isolated colonic Crohn\u2019s disease: the third IBD? Gut. 2017;66:362\u201381.","journal-title":"Gut"},{"key":"1331_CR4","doi-asserted-by":"publisher","first-page":"1982","DOI":"10.1097\/MIB.0000000000000392","volume":"21","author":"SR Vavricka","year":"2015","unstructured":"Vavricka SR, et al. Extraintestinal manifestations of inflammatory bowel disease. Inflamm Bowel Dis. 2015;21:1982\u201392.","journal-title":"Inflamm Bowel Dis"},{"key":"1331_CR5","doi-asserted-by":"publisher","first-page":"6","DOI":"10.3389\/fimmu.2015.00551","volume":"6","author":"I Loddo","year":"2015","unstructured":"Loddo I, Romano C. Inflammatory bowel disease: genetics, epigenetics, and pathogenesis. Front Immunol. 2015;6:6\u201311.","journal-title":"Front Immunol"},{"key":"1331_CR6","doi-asserted-by":"publisher","first-page":"222","DOI":"10.4161\/gmic.24373","volume":"4","author":"SJ Robertson","year":"2013","unstructured":"Robertson SJ, et al. Nod1 and Nod2 signaling does not alter the composition of intestinal bacterial communities at homeostasis. Gut Microbes. 2013;4:222\u201331.","journal-title":"Gut Microbes"},{"key":"1331_CR7","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1038\/ismej.2008.37","volume":"2","author":"J Dicksved","year":"2008","unstructured":"Dicksved J, et al. Molecular analysis of the gut microbiota of identical twins with Crohn\u2019s disease. ISME J. 2008;2:716\u201327.","journal-title":"ISME J"},{"key":"1331_CR8","doi-asserted-by":"publisher","first-page":"1463","DOI":"10.1093\/ibd\/izaa071","volume":"26","author":"AN Ananthakrishnan","year":"2020","unstructured":"Ananthakrishnan AN. Microbiome-based biomarkers for IBD. Inflamm Bowel Dis. 2020;26:1463\u20139.","journal-title":"Inflamm Bowel Dis"},{"key":"1331_CR9","doi-asserted-by":"publisher","first-page":"2174","DOI":"10.1053\/j.gastro.2019.03.017","volume":"156","author":"LJ Cohen","year":"2019","unstructured":"Cohen LJ, Cho JH, Gevers D, Chu H. Genetic factors and the intestinal microbiome guide development of microbe-based therapies for inflammatory bowel diseases. Gastroenterology. 2019;156:2174\u201389.","journal-title":"Gastroenterology"},{"key":"1331_CR10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12876-018-0926-4","volume":"19","author":"F Imhann","year":"2019","unstructured":"Imhann F, et al. Correction: The 1000IBD project: multi-omics data of 1000 inflammatory bowel disease patients; data release 1 (BMC Gastroenterology (2019) 19:5 DOI: 10.1186\/s12876-018-0917-5). BMC Gastroenterol. 2019;19:1\u201310.","journal-title":"BMC Gastroenterol"},{"key":"1331_CR11","doi-asserted-by":"publisher","first-page":"e0246367","DOI":"10.1371\/journal.pone.0246367","volume":"16","author":"L Revilla","year":"2021","unstructured":"Revilla L, et al. Multi-omic modelling of inflammatory bowel disease with regularized canonical correlation analysis. PLoS One. 2021;16:e0246367.","journal-title":"PLoS One"},{"key":"1331_CR12","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1038\/s41586-019-1237-9","volume":"569","author":"J Lloyd-Price","year":"2019","unstructured":"Lloyd-Price J, et al. Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases. Nature. 2019;569:655\u201362.","journal-title":"Nature"},{"key":"1331_CR13","doi-asserted-by":"publisher","first-page":"1524","DOI":"10.1093\/ibd\/izaa183","volume":"26","author":"NZ Borren","year":"2020","unstructured":"Borren NZ, et al. Multi-\"-Omics\" profiling in patients with quiescent inflammatory bowel disease identifies biomarkers predicting relapse. Inflamm Bowel Dis. 2020;26:1524\u201332.","journal-title":"Inflamm Bowel Dis"},{"key":"1331_CR14","first-page":"304","volume":"26","author":"JD Lewis","year":"2020","unstructured":"Lewis JD, et al. Correlation of stool frequency and abdominal pain measures with simple endoscopic score for Crohn\u2019s disease. Inflamm Bowel Dis. 2020;26:304\u201313.","journal-title":"Inflamm Bowel Dis"},{"issue":"2","key":"1331_CR15","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1038\/s41564-021-01050-3","volume":"7","author":"RH Mills","year":"2022","unstructured":"Mills RH, et al. Multi-omics analyses of the ulcerative colitis gut microbiome link Bacteroides vulgatus proteases with disease severity. Nat Microbiol. 2022;7(2):262\u201376.","journal-title":"Nat Microbiol."},{"key":"1331_CR16","doi-asserted-by":"publisher","first-page":"438427","DOI":"10.1101\/2021.04.04.438427","volume":"2021","author":"Q Zhu","year":"2021","unstructured":"Zhu Q, et al. OGUs enable effective, phylogeny-aware analysis of even shallow metagenome community structures. bioRxiv. 2021;2021:438427. https:\/\/doi.org\/10.1101\/2021.04.04.438427.","journal-title":"bioRxiv"},{"key":"1331_CR17","doi-asserted-by":"publisher","first-page":"828","DOI":"10.1038\/nbt.3597","volume":"34","author":"M Wang","year":"2016","unstructured":"Wang M, et al. Sharing and community curation of mass spectrometry data with Global Natural Products Social Molecular Networking. Nat Biotechnol. 2016;34:828\u201337.","journal-title":"Nat Biotechnol"},{"key":"1331_CR18","doi-asserted-by":"publisher","first-page":"e00200","DOI":"10.1128\/mSystems.00200-20","volume":"5","author":"CG Gonzalez","year":"2020","unstructured":"Gonzalez CG, et al. High-throughput stool metaproteomics: method and application to human specimens. mSystems. 2020;5:e00200\u201320.","journal-title":"mSystems"},{"key":"1331_CR19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-019-48495-5","volume":"9","author":"CG Gonzalez","year":"2019","unstructured":"Gonzalez CG, et al. Latent-period stool proteomic assay of multiple sclerosis model indicates protective capacity of host-expressed protease inhibitors. Sci Rep. 2019;9:1\u201315.","journal-title":"Sci Rep"},{"key":"1331_CR20","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1038\/ng.3359","volume":"47","author":"JZ Liu","year":"2015","unstructured":"Liu JZ, et al. Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations. Nat Genet. 2015;47:979\u201386.","journal-title":"Nat Genet"},{"key":"1331_CR21","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1038\/nature05981","volume":"448","author":"JC Hermann","year":"2007","unstructured":"Hermann JC, et al. Structure-based activity prediction for an enzyme of unknown function. Nature. 2007;448:775\u20139.","journal-title":"Nature"},{"key":"1331_CR22","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1136\/gut.2005.073817","volume":"55","author":"C Manichanh","year":"2006","unstructured":"Manichanh C, et al. Reduced diversity of faecal microbiota in Crohn\u2019s disease revealed by a metagenomic approach. Gut. 2006;55:205\u201311.","journal-title":"Gut"},{"key":"1331_CR23","doi-asserted-by":"publisher","first-page":"W90","DOI":"10.1093\/nar\/gkw377","volume":"44","author":"MV Kuleshov","year":"2016","unstructured":"Kuleshov MV, et al. Enrichr: a comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Res. 2016;44:W90\u20137.","journal-title":"Nucleic Acids Res"},{"key":"1331_CR24","doi-asserted-by":"publisher","first-page":"D607","DOI":"10.1093\/nar\/gky1131","volume":"47","author":"D Szklarczyk","year":"2019","unstructured":"Szklarczyk D, et al. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res. 2019;47:D607\u201313.","journal-title":"Nucleic Acids Res"},{"key":"1331_CR25","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1007\/978-94-007-5940-4_7","volume":"66","author":"D Frees","year":"2013","unstructured":"Frees D, Br\u00f8ndsted L, Ingmer H. Bacterial proteases and virulence. Subcell Biochem. 2013;66:161\u201392.","journal-title":"Subcell Biochem"},{"key":"1331_CR26","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1111\/j.1600-0765.1997.tb01393.x","volume":"32","author":"MS Lantz","year":"1997","unstructured":"Lantz MS. Are bacterial proteases important virulence factors? J Periodontal Res. 1997;32:126\u201332.","journal-title":"J Periodontal Res"},{"key":"1331_CR27","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1038\/ismej.2007.52","volume":"1","author":"M Baumgart","year":"2007","unstructured":"Baumgart M, et al. Culture independent analysis of ileal mucosa reveals a selective increase in invasive Escherichia coli of novel phylogeny relative to depletion of Clostridiales in Crohn\u2019s disease involving the ileum. ISME J. 2007;1:403\u201318.","journal-title":"ISME J"},{"key":"1331_CR28","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1007\/s13668-017-0219-5","volume":"6","author":"S Ocvirk","year":"2017","unstructured":"Ocvirk S, O\u2019Keefe SJ. Influence of bile acids on colorectal cancer risk: potential mechanisms mediated by diet - gut microbiota interactions. Curr Nutr Rep. 2017;6:315\u201322.","journal-title":"Curr Nutr Rep"},{"key":"1331_CR29","doi-asserted-by":"publisher","first-page":"1773","DOI":"10.1053\/j.gastro.2011.07.046","volume":"141","author":"KBMS Islam","year":"2011","unstructured":"Islam KBMS, et al. Bile acid is a host factor that regulates the composition of the cecal microbiota in rats. Gastroenterology. 2011;141:1773\u201381.","journal-title":"Gastroenterology"},{"key":"1331_CR30","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1002\/ibd.20783","volume":"15","author":"B Willing","year":"2009","unstructured":"Willing B, et al. Twin studies reveal specific imbalances in the mucosa-associated microbiota of patients with ileal Crohn\u2019s disease. Inflamm Bowel Dis. 2009;15:653\u201360.","journal-title":"Inflamm Bowel Dis"},{"key":"1331_CR31","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1128\/AEM.06858-11","volume":"78","author":"M Lopez-Siles","year":"2012","unstructured":"Lopez-Siles M, et al. Cultured representatives of two major phylogroups of human colonic Faecalibacterium prausnitzii can utilize pectin, uronic acids, and host-derived substrates for growth. Appl Environ Microbiol. 2012;78:420\u20138.","journal-title":"Appl Environ Microbiol"},{"key":"1331_CR32","doi-asserted-by":"publisher","first-page":"841","DOI":"10.3109\/00365521.2015.1008035","volume":"50","author":"KB Gecse","year":"2015","unstructured":"Gecse KB, et al. Impact of disease location on fecal calprotectin levels in Crohn\u2019s disease. Scand J Gastroenterol. 2015;50:841\u20137.","journal-title":"Scand J Gastroenterol"},{"key":"1331_CR33","doi-asserted-by":"publisher","first-page":"778","DOI":"10.3109\/00365521.2012.677953","volume":"47","author":"T Sipponen","year":"2012","unstructured":"Sipponen T, et al. Fecal calprotectin and S100A12 have low utility in prediction of small bowel Crohn\u2019s disease detected by wireless capsule endoscopy. Scand J Gastroenterol. 2012;47:778\u201384.","journal-title":"Scand J Gastroenterol"},{"key":"1331_CR34","doi-asserted-by":"publisher","first-page":"2235","DOI":"10.1111\/j.1572-0241.2004.40369.x","volume":"99","author":"A Zholudev","year":"2004","unstructured":"Zholudev A, Zurakowski D, Young W, Leichtner A, Bousvaros A. Serologic testing with ANCA, ASCA, and anti-OmpC in children and young adults with Crohn\u2019s disease and ulcerative colitis: diagnostic value and correlation with disease phenotype. Am J Gastroenterol. 2004;99:2235\u201341.","journal-title":"Am J Gastroenterol"},{"key":"1331_CR35","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1093\/ecco-jcc\/jjz130","volume":"14","author":"N Pierre","year":"2020","unstructured":"Pierre N, et al. Proteomics highlights common and distinct pathophysiological processes associated with ileal and colonic ulcers in Crohn\u2019s disease. J Crohns Colitis. 2020;14:205\u201315.","journal-title":"J Crohns Colitis"},{"key":"1331_CR36","doi-asserted-by":"publisher","first-page":"1149","DOI":"10.1093\/ecco-jcc\/jjaa033","volume":"14","author":"N Sol\u00e0-Tapias","year":"2020","unstructured":"Sol\u00e0-Tapias N, Vergnolle N, Denadai-Souza A, Barreau F. The interplay between genetic risk factors and proteolytic dysregulation in the pathophysiology of inflammatory bowel disease. J Crohns Colitis. 2020;14:1149\u201361.","journal-title":"J Crohns Colitis"},{"key":"1331_CR37","doi-asserted-by":"publisher","first-page":"1532","DOI":"10.1053\/j.gastro.2020.12.004","volume":"160","author":"HJ Galipeau","year":"2021","unstructured":"Galipeau HJ, et al. Novel fecal biomarkers that precede clinical diagnosis of ulcerative colitis. Gastroenterology. 2021;160:1532\u201345.","journal-title":"Gastroenterology"},{"key":"1331_CR38","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1016\/j.ijmm.2014.02.009","volume":"304","author":"M Lopez-Siles","year":"2014","unstructured":"Lopez-Siles M, et al. Mucosa-associated Faecalibacterium prausnitzii and Escherichia coli co-abundance can distinguish Irritable Bowel Syndrome and Inflammatory Bowel Disease phenotypes. Int J Med Microbiol. 2014;304:464\u201375.","journal-title":"Int J Med Microbiol"},{"key":"1331_CR39","doi-asserted-by":"publisher","first-page":"626232","DOI":"10.3389\/fped.2021.626232","volume":"9","author":"X Zhuang","year":"2021","unstructured":"Zhuang X, et al. Gut microbiota profile in pediatric patients with inflammatory bowel disease: a systematic review. Front Pediatr. 2021;9:626232.","journal-title":"Front Pediatr"},{"key":"1331_CR40","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1016\/j.chom.2015.01.015","volume":"17","author":"K Yasuda","year":"2015","unstructured":"Yasuda K, et al. Biogeography of the intestinal mucosal and lumenal microbiome in the rhesus macaque. Cell Host Microbe. 2015;17:385\u201391.","journal-title":"Cell Host Microbe"},{"key":"1331_CR41","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1016\/j.gie.2015.03.1974","volume":"82","author":"PS Dulai","year":"2015","unstructured":"Dulai PS, Levesque BG, Feagan BG, D\u2019Haens G, Sandborn WJ. Assessment of mucosal healing in inflammatory bowel disease: review. Gastrointest Endosc. 2015;82:246\u201355.","journal-title":"Gastrointest Endosc"},{"key":"1331_CR42","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1128\/mSystems.00337-18","volume":"4","author":"RH Mills","year":"2019","unstructured":"Mills RH, et al. Evaluating Metagenomic Prediction of the Metaproteome in a 4.5-Year Study of a Patient with Crohn\u2019s Disease. mSystems. 2019;4:1\u201320.","journal-title":"mSystems"},{"key":"1331_CR43","doi-asserted-by":"publisher","first-page":"5477","DOI":"10.1038\/s41467-019-13443-4","volume":"10","author":"Q Zhu","year":"2019","unstructured":"Zhu Q, et al. Phylogenomics of 10,575 genomes reveals evolutionary proximity between domains Bacteria and Archaea. Nat Commun. 2019;10:5477.","journal-title":"Nat Commun"},{"key":"1331_CR44","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1038\/s41592-018-0141-9","volume":"15","author":"A Gonzalez","year":"2018","unstructured":"Gonzalez A, et al. Qiita: rapid, web-enabled microbiome meta-analysis. Nat Methods. 2018;15:796\u20138.","journal-title":"Nat Methods"},{"key":"1331_CR45","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1186\/1471-2105-11-395","volume":"11","author":"T Pluskal","year":"2010","unstructured":"Pluskal T, Castillo S, Villar-Briones A, Oresic M. MZmine 2: modular framework for processing, visualizing, and analyzing mass spectrometry-based molecular profile data. BMC Bioinformatics. 2010;11:395.","journal-title":"BMC Bioinformatics"},{"key":"1331_CR46","doi-asserted-by":"publisher","first-page":"1954","DOI":"10.1038\/s41596-020-0317-5","volume":"15","author":"AT Aron","year":"2020","unstructured":"Aron AT, et al. Reproducible molecular networking of untargeted mass spectrometry data using GNPS. Nat Protoc. 2020;15:1954\u201391.","journal-title":"Nat Protoc"},{"key":"1331_CR47","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1038\/s41589-020-00677-3","volume":"17","author":"A Tripathi","year":"2021","unstructured":"Tripathi A, et al. Chemically informed analyses of metabolomics mass spectrometry data with Qemistree. Nat Chem Biol. 2021;17:146\u201351.","journal-title":"Nat Chem Biol"},{"key":"1331_CR48","doi-asserted-by":"publisher","first-page":"e0064421","DOI":"10.1128\/mSystems.00644-21","volume":"6","author":"VM Anderson","year":"2021","unstructured":"Anderson VM, Wendt KL, Najar FZ, McCall L-I, Cichewicz RH. Building natural product libraries using quantitative clade-based and chemical clustering strategies. mSystems. 2021;6:e0064421.","journal-title":"mSystems"},{"key":"1331_CR49","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1038\/s41587-019-0209-9","volume":"37","author":"E Bolyen","year":"2019","unstructured":"Bolyen E, et al. Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. Nat Biotechnol. 2019;37:852\u20137.","journal-title":"Nat Biotechnol"}],"container-title":["Microbiome"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40168-022-01331-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40168-022-01331-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40168-022-01331-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,14]],"date-time":"2023-04-14T19:15:59Z","timestamp":1681499759000},"score":1,"resource":{"primary":{"URL":"https:\/\/microbiomejournal.biomedcentral.com\/articles\/10.1186\/s40168-022-01331-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,24]]},"references-count":49,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["1331"],"URL":"https:\/\/doi.org\/10.1186\/s40168-022-01331-x","relation":{"has-part":[{"id-type":"doi","id":"https:\/\/doi.org\/10.21203\/rs.3.rs-2819038\/v1","asserted-by":"subject"}]},"ISSN":["2049-2618"],"issn-type":[{"value":"2049-2618","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,24]]},"assertion":[{"value":"1 April 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 July 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 August 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All stool was collected with the approval of the University of California San Diego Institutional Research Board, study # 150675. All participants acknowledged their willingness to participate using written forms, which can be reviewed if needed.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"All authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"133"}}