Systems Biology of Competency in Bacteria is Revealed by Applying Novel Data Analytics to the Transcriptome

Vibrio species regulate their natural competency through activation of two transcription factors, TfoX and QstR, involved in the capture of external DNA and its transport into the cell. However, the comprehensive genetic and transcriptional regulatory basis for competency remains unknown. Here, we use a machine-learning approach to decompose Vibrio natriegens' transcriptome into 45 groups of independently modulated sets of genes (iModulons). We discovered that competency depends on the repression of two housekeeping iModulons (iron metabolism and translation) and the activation of six iModulons; including TfoX and QstR, a novel iModulon of unknown function, and three housekeeping iModulons (representing motility, polycations, and ROS responses). Phenotypic screening of 83 gene deletion strains across the six iModulons showed that loss of iModulon function reduces or eliminates competency. New data analytics revealed the transcriptomic basis for competency and its relationship to housekeeping functions. These results provide the genetic basis for systems biology of competency.