Computational prioritization of potential drug targets for human parasitic diseases.

AGÜERO F, BERRIMAN M, BUCKNER FS, HERTZ-FOWLER C, PAIN A, RALPH SA, REYNOLDS A, RIECHERS A, ROOS DS, SHANMUGAM D, SUZUKI T, VERLINDE CL, VAN VOORHIS WC.

Tahoe, California, USA

Conferencia; Drugs Against Protozoan Parasites, Keystone Symposia Conference.; 2007

Keystone Symposia

For the major tropical diseases, chemotherapeutic agents aregenerally inadequate due to limited efficacy, toxicity, and/or drugresistance.  New drugs are urgently needed to help solve thesedeficiencies in our tropical medicine pharmacopeia. The recentavailability of genome sequences for five tropical disease pathogensand the anticipated completion of sequencing of parasitic helminthgenomes create an opportunity to identify potential newchemotherapeutic targets to combat tropical diseases. To capitaliseon this opportunity, we are developing an open-access website toassist scientists to search the genomic information of tropicaldisease pathogens for potential drug targets. The website allowsscientists to prioritize drug targets by interrogating an extensivedatabase with their own preferred criteria. This database willcombine the large volume of existing genomic and bioinformaticinformation for each target organism with both curated andautomatically extracted data from existing literature relevant toeach putative drug target, and the opportunity for ongoinginterpretation and organization by experts in the field. A wealth ofstructural, genetic and inhibitor data is also available fororthologs of the putative targets from model eukaryotes andprokaryotes, and the database is organized to take advantage of thisdata by mapping all genes from the target organisms to orthologousgenes from model organisms. User-assigned numerical weightings for desirable drug-target characteristics are used to rank putative drug targets to create prioritised lists according to the user´spreferences. In addition to providing a resource to facilitatequerying capabilities for interested scientists, substantial efforthas gone into annotation to assist scientists with identifyingcurated high-value chemotherapeutic targets. The database iscurrently available in a web-based format accessible to registeredusers [at https://weight.bio.upenn.edu] and will shortly be made intoan open source database.This project was initiated by and is supported by a collaborativegrant from the Special Programme for Research and Training inTropical Diseases (TDR), World Health Organization.