ConReg: Analysis and Visualization of Conserved Regulatory Networks in Eukaryotes

Transcription factors (TFs) play a fundamental role in cellular regulation by binding to promoter regions of target genes (TGs) in order to control their gene expression. TF-TG networks are widely used as representations of regulatory mechanisms, e.g. for modeling the cellular response to input signals and perturbations. As the experimental identification of regulatory interactions is time consuming and expensive, one tries to use knowledge from related species when studying an organism of interest. Here, we present ConReg, an interactive web application to store regulatory relations for various species and to investigate their level of conservation in related species. Currently, ConReg contains data for eight model organisms. The regulatory relations stored in publicly available databases cover only a small fraction both of the actual interactions and also of the regulatory relations described in the scientific literature. Therefore, we included regulatory relations extracted from PubMed and PubMedCentral using sophisticated text-mining approaches and from binding site predictions into ConReg. We applied ConReg for the investigation of conserved regulatory motifs in D. melanogaster. From the 471 regulatory relations in REDfly our system was able to identify 66 confirmed conserved regulations in at least one vertebrate model organism (H. sapiens, M. musculus, R. norvegicus, D. rerio). The conserved network consists among others of the well studied motifs for eye-development and the pan-bilaterian kernel for heart specification, which are well-known examples for conserved regulatory relations between different organisms. ConReg is available at http://services.bio.ifi.lmu.de/ConReg/ and can be used to analyze and visualize regulatory networks and their conservation among eight model organisms. It also provides direct links to annotations including literature references to potentially conserved regulatory relations.