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Genomic-scale prioritization of drug targets: the TDR Targets database

Abstract

The increasing availability of genomic data for pathogens that cause tropical diseases has created new opportunities for drug discovery and development. However, if the potential of such data is to be fully exploited, the data must be effectively integrated and be easy to interrogate. Here, we discuss the development of the TDR Targets database (http://tdrtargets.org), which encompasses extensive genetic, biochemical and pharmacological data related to tropical disease pathogens, as well as computationally predicted druggability for potential targets and compound desirability information. By allowing the integration and weighting of this information, this database aims to facilitate the identification and prioritization of candidate drug targets for pathogens.

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Figure 1: Searching the TDR Targets database.
Figure 2: Ranking of Mycobacterium tuberculosis targets using the TDR Targets database.

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Acknowledgements

The authors wish to acknowledge all of the investigators who provided the data in the TDR Targets database including those that participated in the survey on drug targets for Human African Trypanosomiasis (HAT survey) conducted during 2007. We would also like to acknowledge Brandeis University MS students P. Bais and B. Coflan for work on the association of targets with compounds; R. L. Stevens (Argonne National Laboratory) for providing data for gene essentiality in bacteria; K. Chaudhary and T. Carlow (New England BioLabs) for integrated C. elegans phenotype data; J. Sacchetini (Texas A&M) for information on known M. tuberculosis drug targets; and M. Schreiber (Novartis Institute for Tropical Diseases, Singapore) and J. Brown (GlaxoSmithKline) for input on integrating data on persistent expressed genes in dormant-stage M. tuberculosis infection. We would also like to acknowledge essential computational infrastructure and genome annotations made available through the OrthoMCL database (supported by the US National Institutes of Health; NIH); GeneDB (supported by the Wellcome Trust); Ensembl (supported by the European Bioinformatics Institute); and EuPathDB (supported by a Bioinformatics Resource Center contract from the US NIH/National Institute of Allergy and Infectious Diseases). The authors also gratefully acknowledge Pfizer Global Research and Development for sharing data related to druggability. This work was supported by grants from the United Nations Development Programme/World Bank/World Health Organization Special Programme for Research and Training in Tropical Diseases.

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Correspondence to Fernán Agüero or Matthew Berriman or Solomon Nwaka or Stuart A. Ralph or David S. Roos or Wesley C. Van Voorhis.

Supplementary information

Supplementary information S1 (box)

Methods for TDRtargets.org (PDF 532 kb)

Supplementary information S2 (figure)

Step-by-step example of TDR Targets database search (PDF 1344 kb)

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FURTHER INFORMATION

BRENDA

Brugia targets ranked by Kumar et al.

EBI Chemigenomics Databases

Medical Structural Genomics of Pathogenic Protozoa

ModBase

OrthoMCL database

Sigma–Aldrich Enzyme Explorer Assay Library

Structural Genomics Consortium

T. brucei query set (DSR VI/11/07)

TDR Targets database

Tuberculosis target prioritization by Hasan et al.

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Agüero, F., Al-Lazikani, B., Aslett, M. et al. Genomic-scale prioritization of drug targets: the TDR Targets database. Nat Rev Drug Discov 7, 900–907 (2008). https://doi.org/10.1038/nrd2684

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