Human transcriptional gene regulatory network compiled from 14 data resources

Abstract

The transcriptional regulatory network (TRN) in a cell orchestrates spatio-temporal expression of genes to generate cellular responses for maintenance, reproduction, development and survival of the cell and its hosting organism. Transcription factors (TF) regulate the expression of their target genes (TG) and are the fundamental units of TRN. Several databases have been developed to catalogue human TRN based on low- and high-throughput experimental and computational studies considering their importance in understanding cellular physiology. However, literature lacks their comparative assessment on the strengths and weaknesses. We compared over 2.2 million regulatory pairs between 1379 TF and 22,518 TG from 14 resources. Our study reveals that the TF and TG were common across data resources but not their regulatory pairs. TF and TG of the regulatory pairs showed weak expression correlation, significant gene ontology overlap, co-citations in PubMed and low numbers of TF-TG pairs representing transcriptional repression relationships. We assigned each TF-TG regulatory pair a combined confidence score reflecting its reliability based on its presence in multiple databases. The assembled TRN contains 2,246,598 TF-TG pairs, of which, 44,284 with information on TF's activating or repressing effects on their TG and is available upon request. This study brings the information about transcriptional regulation scattered over the literature and databases at one place in the form of one of the most comprehensive and complete human TRN assembled to date. It will be a valuable resource for benchmarking TRN prediction tools, and to the scientific community working in functional genomics, gene expression and regulation analysis.