title: Data integration in physiology using Bayes' rule and minimum Bayes' factors: deubiquitylating enzymes in the renal collecting duct.
abstract: A major challenge in physiology is to exploit the many large-scale data sets available from "-omic" studies to seek answers to key physiological questions. In previous studies, Bayes' theorem has been used for this purpose. This approach requires a means to map continuously distributed experimental data to probabilities (likelihood values) to derive posterior probabilities from the combination of prior probabilities and new data. Here, we introduce the use of minimum Bayes' factors for this purpose and illustrate the approach by addressing a physiological question, "Which deubiquitylating enzymes (DUBs) encoded by mammalian genomes are most likely to regulate plasma membrane transport processes in renal cortical collecting duct principal cells?" To do this, we have created a comprehensive online database of 110 DUBs present in the mammalian genome (https://hpcwebapps.cit.nih.gov/ESBL/Database/DUBs/). We used Bayes' theorem to integrate available information from large-scale data sets derived from proteomic and transcriptomic studies of renal collecting duct cells to rank the 110 known DUBs with regard to likelihood of interacting with and regulating transport processes. The top-ranked DUBs were OTUB1, USP14, PSMD7, PSMD14, USP7, USP9X, OTUD4, USP10, and UCHL5. Among these USP7, USP9X, OTUD4, and USP10 are known to be involved in endosomal trafficking and have potential roles in endosomal recycling of plasma membrane proteins in the mammalian cortical collecting duct.
authors.affiliation: School of Basic Medical Science, Beijing University of Chinese Medicine, Beijing, China; and.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Xue
authors.affiliation: School of Basic Medical Science, Beijing University of Chinese Medicine, Beijing, China; and.
authors.forename: Jia-Xu
authors.initials: JX
authors.lastname: Chen
authors.affiliation: Epithelial Systems Biology Laboratory, Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Epithelial Systems Biology Laboratory, Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.|The Catholic University of America, Washington, District of Columbia.
authors.forename: Barbara
authors.initials: B
authors.lastname: Medvar
authors.affiliation: Epithelial Systems Biology Laboratory, Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland; knepperm@nhlbi.nih.gov.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Knepper
mesh_terms: D000818:Animals; D001499:Bayes Theorem; D000072017:Deubiquitinating Enzymes / Q000378:metabolism*; D006801:Humans; D020407:Internet; D007685:Kidney Tubules, Collecting / Q000201:enzymology*; D016013:Likelihood Functions; D008322:Mammals / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D051379:Mice; D011485:Protein Binding; D051381:Rats; D013223:Statistics as Topic
chemical_list: D026901:Membrane Transport Proteins; D000072017:Deubiquitinating Enzymes
keywords: collecting duct; kidney; systems biology; ubiquitin