T-iDT: Tool for Identification of Drug Target in Bacteria and Validation by Mycobacterium Tuberculosis

Article type: Research Article

Authors: Singh, Nitesh Kumar | Selvam, S. Mahalaxmi | Chakravarthy, Paulsharma

Affiliations: S.R.M. Institute of Science and Technology, Chennai, India | School of Genomics, Loyola College, Chennai, India

Note: [] Corresponding author. Tel.: +91 9840075618; E-mail: [email protected]

Abstract: With the completion of the Human Genome Project in 2003, many new projects to sequence bacterial genomes were started and soon many complete bacterial genome sequences were available. The sequenced genomes of pathogenic bacteria provide useful information for understanding host-pathogen interactions. These data prove to be a new weapon in fighting against pathogenic bacteria by providing information about potential drug targets. But the limitation of computational tools for finding potential drug targets has hindered the process and further experimental analysis. There are many in silico approaches proposed for finding drug targets but only few have been automated. One such approach finds essential genes in bacterial genomes with no human homologue and predicts these as potential drug targets. The same approach is used in our tool. T-iDT, a tool for the identification of drug targets, finds essential genes by comparing a bacterial gene set against DEG (Database of Essential Genes) and excludes homologue genes by comparing against a human protein database. The tool predicts both the set of essential genes as well as potential target genes for the given genome. The tool was tested with Mycobacterium tuberculosis and results were validated. With default parameters, the tool predicted 236 essential genes and 52 genes to encode potential drug targets. A pathway-based approach was used to validate these potential drug target genes. The pathway in which the products of these genes are involved was determined. Our analysis shows that almost all these pathways are very essential for the bacterial survival and hence these genes encode possible drug targets. Our tool provides a fast method for finding possible drug targets in bacterial genomes with varying stringency level. The tool will be helpful in finding possible drug targets in various pathogenic organisms and can be used for further analysis in novel therapeutic drug development. The tool can be downloaded from http://www.milser.co.in/research.htm and http://www.srmbioinformatics.edu.in/forum.htm.

Keywords: Comparative genomics, BLAST, essential genes, DEG, drug target, subtractive genomics

Journal: In Silico Biology, vol. 6, no. 6, pp. 485-493, 2006