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Using advanced data integration approaches and systems biology tools, we studied the contribution of CD susceptibility variants and gene expression in distinct peripheral immune cell subsets (CD14+ monocytes and CD4+ T cells) to relevant clinical traits. Our analyses revealed that most clinical traits capturing CD heterogeneity could be associated with CD14+ and CD4+ gene expression rather than disease susceptibility variants. By disentangling the sources of variation, we identified molecular features that could potentially be driving the heterogeneity of various clinical traits of CD patients. Further downstream analyses identified contextual hub proteins such as genes encoding barrier functions, antimicrobial peptides, chemokines, and their receptors, which are either targeted by drugs used in CD or other inflammatory diseases or are relevant to the biological functions implicated in disease pathology. These hubs could be used as cell type\u2013specific targets to treat specific subtypes of CD patients in a more individualized approach based on the underlying biology driving their disease subtypes. Our study highlights the importance of data integration and systems approaches to investigate complex and heterogeneous diseases such as IBD.<\/jats:p>","DOI":"10.1093\/ibd\/izaa281","type":"journal-article","created":{"date-parts":[[2020,12,14]],"date-time":"2020-12-14T05:53:44Z","timestamp":1607925224000},"page":"870-886","source":"Crossref","is-referenced-by-count":48,"title":["Understanding the Molecular Drivers of Disease Heterogeneity in Crohn\u2019s Disease Using Multi-omic Data Integration and Network Analysis"],"prefix":"10.1093","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1907-4491","authenticated-orcid":false,"given":"Padhmanand","family":"Sudhakar","sequence":"first","affiliation":[{"name":"Department of Chronic Diseases, Metabolism and Ageing, Translational Research Center for Gastrointestinal Disorders (TARGID)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bram","family":"Verstockt","sequence":"additional","affiliation":[{"name":"Department of Chronic Diseases, Metabolism and Ageing, Translational Research Center for Gastrointestinal Disorders (TARGID)"},{"name":"University Hospitals Leuven, Department of Gastroenterology and Hepatology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Cremer","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Laboratory of Clinical Immunology, Katholieke Universiteit Leuven , Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sare","family":"Verstockt","sequence":"additional","affiliation":[{"name":"Department of Chronic Diseases, Metabolism and Ageing, Translational Research Center for Gastrointestinal Disorders (TARGID)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o","family":"Sabino","sequence":"additional","affiliation":[{"name":"Department of Chronic Diseases, Metabolism and Ageing, Translational Research Center for Gastrointestinal Disorders (TARGID)"},{"name":"University Hospitals Leuven, Department of Gastroenterology and Hepatology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Ferrante","sequence":"additional","affiliation":[{"name":"Department of Chronic Diseases, Metabolism and Ageing, Translational Research Center for Gastrointestinal Disorders (TARGID)"},{"name":"University Hospitals Leuven, Department of Gastroenterology and Hepatology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9verine","family":"Vermeire","sequence":"additional","affiliation":[{"name":"Department of Chronic Diseases, Metabolism and Ageing, Translational Research Center for Gastrointestinal Disorders 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