Integrating co-regulated gene-groups and pair-wise genome comparisons to automate reconstruction of microbial pathways

Abstract

This paper extends previously described automated techniques by automatically integrating the information about automatically derived co-transcribed gene-groups, functionally similar gene-groups derived using automated pair-wise genome comparisons and automatically derived orthologs (functionally equivalent genes) to derive microbial metabolic pathways. The method integrates automatically derived co-transcribed gene-groups with orthologous and homologous gene-groups (http://www.mcs.kent.edu//spl sim/arvind/orthos.html), the biochemical pathway template available at the KEGG database. (http://www.genome.ad.jp), the enzyme information derived from the SwissProt enzyme database (http://expasy.hcuge.ch/) and Ligand database (http://www.genome.ad.jp). The technique refines existing pathways (based upon network of reactions of enzymes) by associating corresponding non-enzymatic, regulatory, and cotranscribed proteins to enzymes. The technique has been illustrated by deriving a major pathway of M. tuberculosis by comparison with seven microbial genomes including E coli and B. subtilis - two microbes well explored in wet laboratories.