CoryneRegNet 7, the reference database and analysis platform for corynebacterial gene regulatory networks

Abstract

We present the newest version of CoryneRegNet, the reference database for corynebacterial regulatory interactions, available at www.exbio.wzw.tum.de/coryneregnet/. The exponential growth of next-generation sequencing data in recent years has allowed a better understanding of bacterial molecular mechanisms. Transcriptional regulation is one of the most important mechanisms for bacterial adaptation and survival. These mechanisms may be understood via an organism's network of regulatory interactions. Although the Corynebacterium genus is important in medical, veterinary and biotechnological research, little is known concerning the transcriptional regulation of these bacteria. Here, we unravel transcriptional regulatory networks (TRNs) for 224 corynebacterial strains by utilizing genome-scale transfer of TRNs from four model organisms and assigning statistical significance values to all predicted regulations. As a result, the number of corynebacterial strains with TRNs increased twenty times and the back-end and front-end were reimplemented to support new features as well as future database growth. CoryneRegNet 7 is the largest TRN database for the Corynebacterium genus and aids in elucidating transcriptional mechanisms enabling adaptation, survival and infection.

Fig. 1

Overview of the computational reconstruction of TRNs. (a) General concept of regulatory conservation. (b) TRN transfer scheme: The TRN of a model organism (top) and the predicted TRN of the target organism including all transferred regulations (bottom). In the networks, nodes represent the genes and arrows represent the regulatory interactions.

Fig. 2

Schematic of the CoryneRegNet 7 architecture. The processing layer handles the TRN transfer and data parsing. The database access layer manages any query, update, insertion or deletion in the database. The view is responsible for user interaction through the browser. The controller conducts all the communication and data handling among the other three layers.

Fig. 3

Overview of main statistics present in CoryneRegNet. In (a) the pie chart presents the quantities of regulator types in percentages, (b) represents the distribution of the numbers of TFs regulating a gene, (c) presents the distribution of co-regulating TFs, and (d) demonstrates the distribution of HMM profiles lengths.

Fig. 4

Example of a RI. (a) TG (cg0445) and its regulators in table format. (b,c) present the same TG as in (a), but in a graph format with gene-centered layout (b) and an operon-centered layout (c).

Fig. 5

Detailed gene information page. Here, the “Homologous proteins” tab lists homologs of the cg0199 protein in various other organisms.

Fig. 6

Kinds of motif search provided in CoryneRegNet 7. (a) HMM profiles of one organism being used to identify potential binding sites in the upstream region of a gene of interest. (b) HMM profile of interest being used to identify potential binding sites in all genes of an organism.

Fig. 7

Schematic overview of the TRN transfer pipeline.