Reconstruction of a Global Gene Regulatory Network for Streptomyces Coelicolor: Curation, Inference, and Assessment

Abstract

Streptomyces coelicolor A3(2) is a model microorganism for the study of Streptomycetes, antibiotic production, and secondary metabolism in general. However, little effort to globally study its transcription has been made even though S. coelicolor has an outstanding variety of regulators among bacteria. We manually curated 29 years of literature and databases to assemble a meta-curated experimentally-validated gene regulatory network (GRN) with 5386 genes and 9707 regulatory interactions (~41% of the total expected interactions). We performed network inference using several methods (including two proposed here) for motif detection in DNA sequences and GRN inference from transcriptomics to tackle network incompleteness, using a community integration approach to reduce false positives. Further, we contrasted the structural properties and functional architecture of the networks to assess the predictions’ reliability, finding the inference from DNA sequence data to be the most trustworthy. The inferences allowed us to identify putative novel transcription factors for key Streptomyces antibiotic regulatory proteins (SARPs). Finally, we studied the conservation of the system-level components between S. coelicolor and Corynebacterium glutamicum and identified the basal machinery as the common signature between the two organisms. The curated networks were deposited in Abasy Atlas (https://abasy.ccg.unam.mx/) while the inferences are available as supplementary material.