Feedback and Coupled Feedback Loop Identification within KEGG and Reactome Pathway Database

摘要

Each gene regulatory network (GRN) involves a set of DNA components interacting with each other directly or indirectly to control gene expression levels. Several sub-networks appear in a GRN holding feedback loop or coupled feedback loop mechanisms, which possess returning control mechanisms and aim to intervene or enhance certain functional conditions. Many cases have been reported and experimentally verified the existence of feedback loop relationships in transcription regulatory networks. However, most feedback loops were neither directly shown nor easy to be recognized from public pathway databases. In this study, we integrated two well-known pathway databases of KEGG and Reactome by parsing biological pathway maps into a common standard format, and the developed system could identify hidden feedback and coupled feedback loop information automatically through cross-database and cross-map analyses. We integrated and verified all possible cross-regulatory pathways from these two databases by examining each gene appeared in all collected pathway maps. Over 1,500 biological pathway maps were parsed and examined comprehensively, and an on-line web based system was designed for biologists to query any specified gene for its possible feedback relationships. In addition, paralogous gene information was considered for discovering potential coupled feedback loop relationships among various pathways. The built system for identifying hidden cross-linked relationships could facilitate biologists a fast and easy way to discover how many unveiled dynamic patterns of gene regulation maintain the balance of a specific biological function.