title: Identification of inflammatory bowel disease-related proteins using a reverse k-nearest neighbor search.
abstract: Inflammatory bowel disease (IBD) is a chronic disease whose incidence and prevalence increase every year; however, the pathogenesis of IBD is still unclear. Thus, identifying IBD-related proteins is important for understanding its complex disease mechanism. Here, we propose a new and simple network-based approach using a reverse k-nearest neighbor ( R k NN ) search to identify novel IBD-related proteins. Protein-protein interactions (PPI) and Genome-Wide Association Studies (GWAS) were used in this study. After constructing the PPI network, the R k NN search was applied to all of the proteins to identify sets of influenced proteins among their k-nearest neighbors ( R k NNs ). An observed protein whose influenced proteins were mostly known IBD-related proteins was statistically identified as a novel IBD-related protein. Our method outperformed a random aspect, k NN search, and centrality measures based on the network topology. A total of 39 proteins were identified as IBD-related proteins. Of these proteins, 71% were reported at least once in the literature as related to IBD. Additionally, these proteins were found over-represented in the IBD pathway and enriched in importantly functional pathways in IBD. In conclusion, the R k NN search with the statistical enrichment test is a great tool to identify IBD-related proteins to better understand its complex disease mechanism.
authors.affiliation: Department of Mathematics, Faculty of Applied Science, King Mongkut's University of Technology North Bangkok, 1518 Pracharat 1 Road, Wongsawang, Bangsue, Bangkok 10800, Thailand.
authors.forename: Apichat
authors.initials: A
authors.lastname: Suratanee
authors.forename: Kitiporn
authors.initials: K
authors.lastname: Plaimas
mesh_terms: D019295:Computational Biology / Q000379:methods*; D055106:Genome-Wide Association Study; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000378:metabolism*; D053614:Janus Kinase 2 / Q000235:genetics / Q000378:metabolism; D025941:Protein Interaction Mapping / Q000379:methods; D011506:Proteins / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D011506:Proteins; D018123:Receptors, Interleukin; C492510:interleukin-20 receptor; C507924:JAK2 protein, human; D053614:Janus Kinase 2
keywords: Inflammatory bowel disease; disease-related protein; protein–protein interaction network; reverse k-nearest neighbor search