Yang Tzu-Hsien, Wang Chung-Ching, Wang Yu-Chao, Wu Wei-Sheng
Department of Electrical Engineering, National Cheng Kung University, Tainan, Taiwan and Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan.
Database (Oxford). 2014 Mar 7;2014:bau014. doi: 10.1093/database/bau014. Print 2014.
Regulatory targets of transcription factors (TFs) can be identified by the TF perturbation experiments, which reveal the expression changes owing to the perturbation (deletion or overexpression) of TFs. But the identified targets of a given TF consist of both direct and indirect regulatory targets. It has been shown that most of the TFPE-identified regulatory targets are indirect, indicating that TF-gene regulation is mainly through transcriptional regulatory pathways (TRPs) consisting of intermediate TFs. Without identification of these TRPs, it is not easy to understand how a TF regulates its indirect targets. Because there is no such database depositing the potential TRPs for Saccharomyces cerevisiae now, this motivates us to construct the YTRP (Yeast Transcriptional Regulatory Pathway) database. For each TF-gene regulatory pair under different experimental conditions, all possible TRPs in two underlying networks (constructed using experimentally verified TF-gene binding pairs and TF-gene regulatory pairs from the literature) for the specified experimental conditions were automatically enumerated by TRP mining procedures developed from the graph theory. The enumerated TRPs of a TF-gene regulatory pair provide experimentally testable hypotheses for the molecular mechanisms behind a TF and its regulatory target. YTRP is available online at http://cosbi3.ee.ncku.edu.tw/YTRP/. We believe that the TRPs deposited in this database will greatly improve the usefulness of TFPE data for yeast biologists to study the regulatory mechanisms between a TF and its knocked-out targets. Database URL: http://cosbi3.ee.ncku.edu.tw/YTRP/.
转录因子(TFs)的调控靶标可通过TF扰动实验来确定,该实验揭示了由于TF的扰动(缺失或过表达)而导致的表达变化。但是,给定TF的已确定靶标包括直接和间接调控靶标。研究表明,大多数通过TF扰动实验确定的调控靶标都是间接的,这表明TF-基因调控主要是通过由中间TF组成的转录调控途径(TRP)进行的。如果不识别这些TRP,就不容易理解TF如何调控其间接靶标。由于目前没有这样一个数据库来存储酿酒酵母的潜在TRP,这促使我们构建酵母转录调控途径(YTRP)数据库。对于不同实验条件下的每个TF-基因调控对,通过从图论发展而来的TRP挖掘程序,在两个基础网络(使用实验验证的TF-基因结合对和文献中的TF-基因调控对构建)中自动列举出指定实验条件下的所有可能TRP。TF-基因调控对的列举出的TRP为TF及其调控靶标背后的分子机制提供了可实验验证的假设。YTRP可在网上获取,网址为http://cosbi3.ee.ncku.edu.tw/YTRP/。我们相信,该数据库中存储的TRP将大大提高TF扰动实验数据对酵母生物学家研究TF与其敲除靶标之间调控机制的有用性。数据库网址:http://cosbi3.ee.ncku.edu.tw/YTRP/。