Target identification by phylogenetic
From DrugPedia: A Wikipedia for Drug discovery
== Target identification using phylogenetic profiling:
By performing standard program BLAST, we can search homologos in distant species like bacteria, archea and eukaryotes. It is also easy to reveal the function of significant homologos. However, these sequence comparison methods are of little help, when the proteins lack any significant homologs in the database or gives hits to homologs which are also uncharacterized. Phylogenetic profiling has been used to address this limitation to some extent by at least providing the partial functional information by determining the pathway or the complex to which the protein belongs . The Phylogenetic profiling is the study of co-occurrence of genes across various species. It is based on the assumption that there is strong pressure on the functionally interacting proteins to be co-inherited during speciation. Each gene is represented by a phylogenetic profile, which encodes the presence or absence of genes across the studied organisms. The proteins with identical or similar profiles phylogenetic profiles are found to be participating in common pathways or the functional complex.
The genes that are universally conserved are assumed to be performing the housekeeping functions whereas the genes that are specifically found in only a organism or a group of organisms may be involved in highly specialized functions specific for the organism/s. The ABC- transporters of Mycobacterium tuberculosis are found to be highly conserved across large number of bacteria whereas its Pro-Glu(PE)/Pro-Pro-Glu(PPE) family genes, over 200 genes are annotated as encoding enzymes for the metabolism of fatty acids are specific to organisms of the Mycobacterium complex suggesting their possible role in pathogenesis. In case of pathogens, these highly specific genes may confer certain traits that help the pathogen to combat the immune system of the host and hence prove to be important targets for the drug development. Phylogenetic profiling can thus be useful to explore the novel and known targets from the Mycobacterium.
