title: Essential gene identification and drug target prioritization in Leishmania species.
abstract: Leishmaniasis is one of the neglected tropical diseases (NTDs), mainly affecting impoverished communities and having varied ranges of pathogenicity according to the diverse spectrum of clinical manifestations. It is endemic in many countries and poses major challenges to healthcare systems in developing countries. Despite the fact that most of the current mono and combination therapies are found to be failures, clear perception of gene essentiality for parasite survival are now desideratum to identify potential biochemical targets through selection. Here we used the metabolic network of L. major, to perform a comprehensive set of in silico deletion mutants and have systematically recognized a clearly defined set of essential proteins by combining several essential criteria. In this paper we summarize the efforts to prioritize potential drug targets up to a five-fold enrichment compared with a random selection.
authors.affiliation: Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar, Mohali, India-160062. mesophia@niper.ac.in.
authors.forename: M L Stanly
authors.initials: ML
authors.lastname: Paul
authors.forename: Amandeep
authors.initials: A
authors.lastname: Kaur
authors.forename: Ankit
authors.initials: A
authors.lastname: Geete
authors.forename: M Elizabeth
authors.initials: ME
authors.lastname: Sobhia
mesh_terms: D000981:Antiprotozoal Agents / Q000494:pharmacology*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D016503:Drug Delivery Systems; D004843:Epistasis, Genetic / Q000187:drug effects; D017353:Gene Deletion; D055786:Gene Knockout Techniques; D020043:Genes, Essential; D005978:Glutathione / Q000378:metabolism; D007891:Leishmania / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics*; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D008958:Models, Molecular; D008970:Molecular Weight; D009247:NADH, NADPH Oxidoreductases / Q000737:chemistry / Q000378:metabolism; D054778:NM23 Nucleoside Diphosphate Kinases / Q000737:chemistry / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D055503:Protein Multimerization / Q000187:drug effects; D015800:Protozoan Proteins / Q000378:metabolism; D040681:Structural Homology, Protein
chemical_list: D000981:Antiprotozoal Agents; D054778:NM23 Nucleoside Diphosphate Kinases; D015800:Protozoan Proteins; D009247:NADH, NADPH Oxidoreductases; C049608:trypanothione reductase; D005978:Glutathione