Xue Zhe, Chen Jia-Xu, Zhao Yue, Medvar Barbara, Knepper Mark A
School of Basic Medical Science, Beijing University of Chinese Medicine, Beijing, China; and.
Epithelial Systems Biology Laboratory, Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
Physiol Genomics. 2017 Mar 1;49(3):151-159. doi: 10.1152/physiolgenomics.00120.2016. Epub 2016 Dec 30.
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.
生理学面临的一项重大挑战是利用“组学”研究中可得的众多大规模数据集，来寻找关键生理学问题的答案。在以往研究中，贝叶斯定理已被用于此目的。这种方法需要一种手段，将连续分布的实验数据映射为概率（似然值），以便从先验概率和新数据的组合中推导出后验概率。在此，我们引入最小贝叶斯因子用于此目的，并通过解决一个生理学问题来阐述该方法：“哺乳动物基因组编码的哪些去泛素化酶（DUBs）最有可能调节肾皮质集合管主细胞中的质膜转运过程？”为此，我们创建了一个包含哺乳动物基因组中110种DUBs的综合在线数据库（https://hpcwebapps.cit.nih.gov/ESBL/Database/DUBs/）。我们使用贝叶斯定理整合来自肾集合管细胞蛋白质组学和转录组学研究的大规模数据集的可用信息，以对110种已知的DUBs与转运过程相互作用并进行调节的可能性进行排名。排名靠前的DUBs有OTUB1、USP14、PSMD7、PSMD14、USP7、USP9X、OTUD4、USP10和UCHL5。其中，USP7、USP9X、OTUD4和USP10已知参与内体运输，并且在哺乳动物皮质集合管中质膜蛋白的内体再循环中具有潜在作用。
