EGRIN 2.0 is a systems-level model that delineates the complex relationship between environment, gene regulation, and phenotype in prokaryotes

Why EGRIN 2.0?

A foremost challenge in systems biology is to understand how just a few transcription factors (TFs) in a microbial genome generate a wide array of nuanced responses to varied environmental challenges. EGRIN 2.0 is a new model for the complete gene regulatory network (GRN) of a prokaryote. This model is reverse engineered directly from gene expression data and genomic sequence, and hence the methodology to generate EGRIN 2.0 is applicable to any prokaryotic organism.

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The EGRIN 2.0 model demonstrates how environmental response programs are encoded in the distribution and complex organizations of cis-acting gene regulatory elements (GREs) across an entire prokaryotic genome. EGRIN 2.0 is remarkably accurate. It rediscovered the E. coli GRN governed by nearly two-thirds of its characterized TFs that have been carefully curated in RegulonDB from decades of work by numerous laboratories.

Strikingly, in addition to accurately recapitulating the architecture of well-characterized promoters in canonical locations, the model also revealed that there is widespread regulation at non-canonical locations –within genes and operons! The EGRIN 2.0 model also predicts the context and combinations in which TFs act at GREs in these canonical and non-canonical locations to coordinate transcription across the entire genome, to reorganize functionally-related genes from different operons and regulons into conditionally co-regulated modules or corems. Remarkably, corems capture fitness-relevant gene-gene associations that are NOT attributable to regulons, operons, or combinatorial control mechanisms!

We have inferred comprehesive models for two prokaryotic organisms: a bacterium (Escherichia coli K-12) and an archaeon (Halobacterium salinarum NRC-1).

This website facilitates targeted and exploratory investigation of the model's predictions.

Highlights from the paper

Genes

Organism Gene Supporting Figure
E. coli carA (b0032) Figure 2
E. coli pyrL (b4246) Figure S3
H. salinarum kdpA (VNG6176G) Figure 2
H. salinarum dppA (VNG2349G) Figure 3

Corems

Organism Corem Supporting Figure
E. coli nucleotide corem (ec516031) Figure 4
E. coli purine corem (ec516034) Figure 4
E. coli pyrimidine corem (ec512157) Figure 4
H. salinarum dpp corem (hc21645) Figure 3
H. salinarum dpp leader corem (hc6326) Figure 3
H. salinarum dpp permease corem (hc21279) Figure 3