Liu Zhi-Ping, Wu Canglin, Miao Hongyu, Wu Hulin
Department of Biomedical Engineering, School of Control Science and Engineering, Shandong University, Jinan, Shandong 250061, China and.
Department of Biostatistics, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Database (Oxford). 2015 Sep 30;2015. doi: 10.1093/database/bav095. Print 2015.
Transcriptional and post-transcriptional regulation of gene expression is of fundamental importance to numerous biological processes. Nowadays, an increasing amount of gene regulatory relationships have been documented in various databases and literature. However, to more efficiently exploit such knowledge for biomedical research and applications, it is necessary to construct a genome-wide regulatory network database to integrate the information on gene regulatory relationships that are widely scattered in many different places. Therefore, in this work, we build a knowledge-based database, named 'RegNetwork', of gene regulatory networks for human and mouse by collecting and integrating the documented regulatory interactions among transcription factors (TFs), microRNAs (miRNAs) and target genes from 25 selected databases. Moreover, we also inferred and incorporated potential regulatory relationships based on transcription factor binding site (TFBS) motifs into RegNetwork. As a result, RegNetwork contains a comprehensive set of experimentally observed or predicted transcriptional and post-transcriptional regulatory relationships, and the database framework is flexibly designed for potential extensions to include gene regulatory networks for other organisms in the future. Based on RegNetwork, we characterized the statistical and topological properties of genome-wide regulatory networks for human and mouse, we also extracted and interpreted simple yet important network motifs that involve the interplays between TF-miRNA and their targets. In summary, RegNetwork provides an integrated resource on the prior information for gene regulatory relationships, and it enables us to further investigate context-specific transcriptional and post-transcriptional regulatory interactions based on domain-specific experimental data. Database URL: http://www.regnetworkweb.org.
基因表达的转录和转录后调控对于众多生物过程至关重要。如今,各种数据库和文献中已记录了越来越多的基因调控关系。然而,为了更有效地将这些知识用于生物医学研究和应用,有必要构建一个全基因组调控网络数据库,以整合广泛分散在许多不同地方的基因调控关系信息。因此,在这项工作中,我们通过收集和整合来自25个选定数据库的转录因子(TFs)、微小RNA(miRNAs)与靶基因之间已记录的调控相互作用,构建了一个名为“RegNetwork”的基于知识的人类和小鼠基因调控网络数据库。此外,我们还基于转录因子结合位点(TFBS)基序推断并纳入了潜在的调控关系到RegNetwork中。结果,RegNetwork包含了一组全面的实验观察到的或预测的转录和转录后调控关系,并且数据库框架设计灵活,便于未来潜在扩展以纳入其他生物体的基因调控网络。基于RegNetwork,我们表征了人类和小鼠全基因组调控网络的统计和拓扑特性,我们还提取并解释了涉及TF-miRNA及其靶标之间相互作用的简单而重要的网络基序。总之,RegNetwork提供了关于基因调控关系先验信息的整合资源,并且使我们能够基于特定领域的实验数据进一步研究特定背景下的转录和转录后调控相互作用。数据库网址:http://www.regnetworkweb.org。