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Supergenomic network compression and the discovery of EXP1 as a glutathione transferase inhibited by artesunate.

Cell | 2014

A central problem in biology is to identify gene function. One approach is to infer function in large supergenomic networks of interactions and ancestral relationships among genes; however, their analysis can be computationally prohibitive. We show here that these biological networks are compressible. They can be shrunk dramatically by eliminating redundant evolutionary relationships, and this process is efficient because in these networks the number of compressible elements rises linearly rather than exponentially as in other complex networks. Compression enables global network analysis to computationally harness hundreds of interconnected genomes and to produce functional predictions. As a demonstration, we show that the essential, but functionally uncharacterized Plasmodium falciparum antigen EXP1 is a membrane glutathione S-transferase. EXP1 efficiently degrades cytotoxic hematin, is potently inhibited by artesunate, and is associated with artesunate metabolism and susceptibility in drug-pressured malaria parasites. These data implicate EXP1 in the mode of action of a frontline antimalarial drug.

Pubmed ID: 25126794 RIS Download

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Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: AI109023
  • Agency: NIH HHS, United States
    Id: DP2 OD001315
  • Agency: NIGMS NIH HHS, United States
    Id: GM079656
  • Agency: NIGMS NIH HHS, United States
    Id: P50 GM071508
  • Agency: NIH HHS, United States
    Id: 1DP2OD001315-01
  • Agency: NIAID NIH HHS, United States
    Id: R37 AI050234
  • Agency: Intramural NIH HHS, United States
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM079656
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI050234
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM066099
  • Agency: NIAID NIH HHS, United States
    Id: AI50234
  • Agency: NIGMS NIH HHS, United States
    Id: GM066099
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI109023

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AmiGO (tool)

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