Integration of Molecular Interactome and Targeted Interaction Analysis to Identify a COPD Disease Network Module
Year: 2018
Type: article
Abstract: The polygenic nature of complex diseases offers potential opportunities to utilize network-based approaches that leverage the comprehensive set of protein-protein interactions (the human interactome) to identify new genes of interest and relevant biological pathways. However, the incompleteness of the current human interactome prevents it from reaching its full potential to extract network-based knowledge from gene discovery efforts, such as genome-wide association studies, for complex diseases like chronic obstructive pulmonary disease (COPD). Here, we provide a framework that integrates the existing human interactome information with experimental protein-protein interaction data for FAM13A, one of the most highly associated genetic loci to COPD, to find a more comprehensive disease network module. We identified an initial disease network neighborhood by applying a random-walk method. Next, we developed a network-based closeness approach (C AB ) that revealed 9 out of 96 FAM13A interacting partners identified by affinity purification assays were significantly close to the initial network neighborhood. Moreover, compared to a similar method (local radiality), the C AB approach predicts low-degree genes as potential candidates. The candidates identified by the network-based closeness approach were combined with the initial network neighborhood to build a comprehensive disease network module (163 genes) that was enriched with genes differentially expressed between controls and COPD subjects in alveolar macrophages, lung tissue, sputum, blood, and bronchial brushing datasets. Overall, we demonstrate an approach to find disease-related network components using new laboratory data to overcome incompleteness of the current interactome.
Source: Scientific Reports
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,690
Funders: U.S. Department of Health and Human Services, U.S. Department of Veterans Affairs, Pfizer, AstraZeneca, GlaxoSmithKline, COPD Foundation, Sunovion, National Institutes of Health, Agency for Healthcare Research and Quality, Centers for Medicare and Medicaid Services, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Institute of Environmental Health Sciences, Army Research Office
Awards: G1113415418, CLINICAL CENTER FOR THE LUNG VOLUME REDUCTION SURGERY, G1207659464, G1220799682, LUNG VOLUME REDUCTION STUDY--CLINICAL CENTER, G1356451498, G1410957586, G1439225947, G1576662596, G1605453878, G1615620936, G1617588125, G1651414227, CLINICAL CENTER FOR LVRS, G1735610881, CLNICAL CENTER FOR LVRS, CLNICAL CENTER FOR LVRS, G182694510, LUNG VOLUME REDUCTION STUDY--CLINICAL CENTER, Identifying Genetic Determinants of Severe, Early-Onset COPD, LUNG VOLUME REDUCTION SURGERY--CLINICAL CENTER, G226397431, LUNG VOLUME REDUCTION SURGERY--CLINICAL CENTER, G2412257637, G2417563097, LUNG VOLUME REDUCTION SURGERY--CLINICAL CENTER, G2558926142, LUNG VOLUME REDUCTION SURGERY--CLINICAL CENTER, G2583773487, G2599011918, G278468722, G3110798224, G3141641755, G3146753889, CLINICAL COORDINATING CENTER FOR LVRS, Systems Biology of Airway Disease, G3502822211, Integrative Genomics of Acute Asthma Control, G3715945925, G3805264881, G3842720522, G3874500373, G4089291197, G4153249725, G4255341634, G4606287987, G4679503075, G468516202, G48533833, G5181772611, G520825964, G5258357286, G5391864042, G5484345081, G556935766, The Genetic Epidemiology of Asthma in Costa Rica, Functional Genetics of COPD, (2 of 2) Genetic Epidemiology of COPD, G5791858519, G6093809360, G6315211796, CLNICAL CENTER FOR THE LVRS, Community Assist of Southern Arizona, G6570314638, G657448715, LUNG VOLUME REDUCTION SURGERY--CLINICAL CENTER, CLINICAL CENTER FOR LVRS, (1 of 2) Genetic Epidemiology of COPD, CLINICAL CENTER FOR THE LUNG VOLUME REDUCTION SURGERY, G6996658085, G7092741763, G7218825848, G7437034880, G7452299184, G7527338881, G7541302268, G754838926, Using Networks to Assign Gene Function in Lung Disease, G778147052, G7949433598, G8081622010, Genomic Analysis of Network Perturbations in Human Disease, Metabolic Control of Stemness in lung epithelial progenitors by FAM13A, G8354759825, G8643874822, G8819318481, G8938195782, LUNG VOLUME REDUCTION SURGERY--CLINICAL CENTER, G9000091268, G9000161611, G9000213766, G9000218965, G9000228787, G9000292435, Distinct and Overlapping Pathways of Fibrosis and Emphysema in Cigarette Smokers, CLINICAL CENTER FOR THE LUNG VOLUME REDUCTION SURGERY, CLINICAL CENTER FOR THE LUNG VOLUME REDUCTION SURGERY, G943488547, G993448119
OpenAlex ID: W2891871137