Human transcriptional gene regulatory network compiled from 14 data resources

Abstract

Transcriptional regulatory network (TRN) orchestrates spatio-temporal expression of genes to generate cellular responses for survival. The transcription factors (TF) regulating expression of their target genes (TG) 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 comparative assessment on the strength and weakness of each database. In this study, we compared over 2.2 million regulatory pairs between 1,379 TF and 22,518 TG assembled from 14 data resources. Our study reveals that the TF and TG were common across data resources but not their regulatory pairs. We observed that the 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. Furthermore, each TF-TG regulatory pair assigned a combined confidence score reflecting its reliability based on its presence in multiple databases and co-expression. The TRN containing 2,246,598 TF-TG pairs, of which, 44,284 with the information on TFs activating or repressing effects on their TG 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 TRNs assembled to date, which will be a valuable resource for benchmarking TRN prediction tools, and to the scientific community working in functional genomics, gene expression and gene regulation analysis.