Bayesian decomposition analysis of bacterial phylogenomic profiles.
BACKGROUND
The past two decades have seen the appearance of new infectious diseases and the reemergence of old diseases previously thought to be under control. At the same time, the effectiveness of the existing antibacterials is rapidly decreasing due to the spread of multidrug-resistant pathogens.


OBJECTIVE
The aim of this study was to the identify candidate molecular targets (e.g. enzymes) within essential metabolic pathways specific to a significant subset of bacterial pathogens as the first step in the rational design of new antibacterial drugs.


METHODS
We constructed a dataset of phylogenomic profiles (vectors that encode the similarity, measured by BLAST scores, of a gene across many species) for a series of 31 pathogenic bacteria of interest with 1073 genes taken from the reference organisms Escherichia coli and Mycobacterium tuberculosis. We applied Bayesian Decomposition, a matrix decomposition algorithm, to identify functional metabolic units comprising overlapping sets of genes in this dataset.


RESULTS
Although no information on phylogeny was provided to the system, Bayesian Decomposition retrieved the known bacteria phylogenic relationships on the basis of the proteins necessary for survival. In addition, a set of genes required by all bacteria was identified, as well as components and enzymes specific to subsets of bacteria.


CONCLUSIONS
The use of phylogenomic profiles and Bayesian Decomposition provide important insights for the design of new antibacterial therapeutics.
Bidaut
Ghislain
G
Division of Population Science, Bioinformatics, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Suhre
Karsten
K
Claverie
Jean-Michel
JM
Ochs
Michael F
MF
D000465:Algorithms; D000900:Anti-Bacterial Agents / Q000145:classification; D001499:Bayes Theorem; D016680:Genome, Bacterial; D008957:Models, Genetic; D010802:Phylogeny
D000900:Anti-Bacterial Agents