CMRegNet-An interspecies reference database for corynebacterial and mycobacterial regulatory networks

Abstract

Background: Organisms utilize a multitude of mechanisms for responding to changing environmental conditions, maintaining their functional homeostasis and to overcome stress situations. One of the most important mechanisms is transcriptional gene regulation. In-depth study of the transcriptional gene regulatory network can lead to various practical applications, creating a greater understanding of how organisms control their cellular behavior.

Description: In this work, we present a new database, CMRegNet for the gene regulatory networks of Corynebacterium glutamicum ATCC 13032 and Mycobacterium tuberculosis H37Rv. We furthermore transferred the known networks of these model organisms to 18 other non-model but phylogenetically close species (target organisms) of the CMNR group. In comparison to other network transfers, for the first time we utilized two model organisms resulting into a more diverse and complete network of the target organisms.

Conclusion: CMRegNet provides easy access to a total of 3,103 known regulations in C. glutamicum ATCC 13032 and M. tuberculosis H37Rv and to 38,940 evolutionary conserved interactions for 18 non-model species of the CMNR group. This makes CMRegNet to date the most comprehensive database of regulatory interactions of CMNR bacteria. The content of CMRegNet is publicly available online via a web interface found at http://lgcm.icb.ufmg.br/cmregnet .

Fig. 1

Binding sites pipeline. (a) Table from TBDB with relation (gene target – regulator) and their respective coordinates; (b) GenomeView to visualize in the genomic context; (c) The different cases of inconsistency: (i) Overlap - When it has the overlapping region with neighbour’s intragenic regions; (ii) Distance - When the region is more distant than the chosen threshold; (iii) Size - When the size transcends the threshold; (iv) Operon - case where peak regions are intraoperon; and (d) Output file, each multi-FASTA corresponds a regulator

Fig. 2

Schematic overview illustrating the retrieval of binding sites information of both model organisms M. tuberculosis H37Rv and C. glutamicum ATCC 13032 using TBDB and CoryneRegNet as main sources

Fig 3

The expandable list summarizes the relevant data for the reconstruction of regulatory networks of the gene Rv0081 of M. tuberculosis. (a) The operon membership of the selected gene; (b) gene/protein information, providing links to the genome annotation deposited at the NCBI; (c/d/e) regulations, summarizing all available information on the gene regulatory network of the selected gene; (f) attributes, providing PSSMs and sequence logos of the predicted Rv0081 binding sites consensus. The height of each letter within an individual stack represents the nucleotide’s frequency relative to the particular motif position; thus, the stack according to the respective position indicates the degree of a nucleotide’s conservation

Fig. 4

Reconstruction of the gene network of Rv0081 of M. tuberculosis. The figure shows different levels of regulation. (a), (b), and (c) were created using a cut-off of 3, 2 and 1 respectively. The layout of (c) is circular, of (a) and (b) organic. The computed results showed that Rv0081 regulated 25 genes and a single regulator was identified for this gene, using a cut-off 1 (c)

Fig. 5

Screenshot of GraphVis after the manual integration of eleven additional genes