Detection of biochemical pathways by probabilistic matching of phyletic vectors

A phyletic vector, also known as a phyletic (or phylogenetic) pattern, is a binary representation of the presences and absences of orthologous genes in different genomes. Joint occurrence of two or more genes in many genomes results in closely similar binary vectors representing these genes, and this similarity between gene vectors may be used as a measure of functional association between genes. Better understanding of quantitative properties of gene co-occurrences is needed for systematic studies of gene function and evolution. We used the probabilistic iterative algorithm Psi-square to find groups of similar phyletic vectors. An extended Psi-square algorithm, in which pseudocounts are implemented, shows better sensitivity in identifying proteins with known functional links than our earlier hierarchical clustering approach. At the same time, the specificity of inferring functional associations between genes in prokaryotic genomes is strongly dependent on the pathway: phyletic vectors of the genes involved in energy metabolism and in de novo biosynthesis of the essential precursors tend to be lumped together, whereas cellular modules involved in secretion, motility, assembly of cell surfaces, biosynthesis of some coenzymes, and utilization of secondary carbon sources tend to be identified with much greater specificity. It appears that the network of gene coinheritance in prokaryotes contains a giant connected component that encompasses most biosynthetic subsystems, along with a series of more independent modules involved in cell interaction with the environment.