Open AccessSystems analysis of metabolism in the pathogenic trypanosomatid Leishmania major
Author(s) -
Chavali Arvind K,
Whittemore Jeffrey D,
Eddy James A,
Williams Kyle T,
Papin Jason A
Publication year - 2008
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.1038/msb.2008.15
Subject(s) - biology , amastigote , computational biology , robustness (evolution) , metabolic network , leishmania , gene , organism , model organism , systems biology , gene regulatory network , genetics , computer science , gene expression , parasite hosting , world wide web
Systems analyses have facilitated the characterization of metabolic networks of several organisms. We have reconstructed the metabolic network of Leishmania major , a poorly characterized organism that causes cutaneous leishmaniasis in mammalian hosts. This network reconstruction accounts for 560 genes, 1112 reactions, 1101 metabolites and 8 unique subcellular localizations. Using a systems‐based approach, we hypothesized a comprehensive set of lethal single and double gene deletions, some of which were validated using published data with approximately 70% accuracy. Additionally, we generated hypothetical annotations to dozens of previously uncharacterized genes in the L. major genome and proposed a minimal medium for growth. We further demonstrated the utility of a network reconstruction with two proof‐of‐concept examples that yielded insight into robustness of the network in the presence of enzymatic inhibitors and delineation of promastigote/amastigote stage‐specific metabolism. This reconstruction and the associated network analyses of L. major is the first of its kind for a protozoan. It can serve as a tool for clarifying discrepancies between data sources, generating hypotheses that can be experimentally validated and identifying ideal therapeutic targets.