GENOMICS A High-Salt Lifestyle

Bonneau et al. describe progress in an effort to link systems-level analysis to events at the molecular and organismal levels. Using experiments and computation, they have pooled transcriptome, protein-protein interaction, structural, and evolution-related data to generate a dynamic model of the halophilic organism Halobacterium salinarum. This model was trained on data sets that included more than 200 microarray experiments measuring responses to genetic perturbations and environmental factors (oxygen, sunlight, transition metals, ultraviolet radiation, and desiccation and rehydration). The model, known as EGRIN (environment and gene regulatory influence network) represents transcriptional regulation for 1929 of the 2400 genes in H. salinarum, and it was used to predict transcriptional changes after environmental or genetic perturbations (or combinations thereof) that had been held out of the training data sets. As an example, the gene nhaC3 encodes a Na+ extrusion pump that allows this organism to grow under high-salt conditions. Analyses of a map of protein-DNA interactions generated from ChIP-chip data could not dissect which of five possible transcriptional regulators governed expression of the gene, yet one of these was predicted by EGRIN to have the strongest effect, which was confirmed in laboratory experiments.


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A Predictive Model for Transcriptional Control of Physiology in a Free Living Cell
Cell 2007 131: 1354-1365