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 TDRtargets.org 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 prioritisation of candidate drug targets for pathogens.

Advances in Antimalarial Drug Evaluation and New Targets for Antimalarials

“…Databases such as TDR targets (http://tdrtargets.org) gather information on putative targets for several pathogens including Plasmodium, providing tools for their prioritization in whole genomes depending on user queries (Aguero et al, 2008). The Protein Data Bank (www.pdb.org) is also a useful resource, providing data on proteins whose 3D-structures have been solved experimentally by using either X-Rays or NMR.…”

Novel Drug Targets for Food-Borne PathogenCampylobacter jejuni: An Integrated Subtractive Genomics and Comparative Metabolic Pathway Study

“…Gene essentiality is also thought to be an important criteria for identification of therapeutic drug targets (Agüero et al, 2008). But there is a limitation to this approach as it fails to identify some targets such as hypoxanthine phosphoribosyl transferase as essential in Plasmodium falciparum (false negative) (Winzeler et al, 1999), while sometimes it yields false positives as in the case of dihydrofolate reductase in Leishmania major (Titus et al, 1995).…”

“…In our study, we have utilized a subtractive genomics approach to predict genes essential to C. jejuni through homology search against experimentally predicted essentiality data from C. jejuni and H. pylori in DEG, both of which belong to the epsilon class of proteobacteria. Significant advancements in genome sequencing and bioinformatics coupled with experimental data have shown that factors which are determinant of structural and molecular properties of proteins, such as molecular weight, subcellular localization, transmembrane prediction, and availability of 3D structure, can aid in prioritization of drug targets (Agüero et al, 2008) and maximize the likelihood of landing to the best therapeutic target against pathogen, considerably reducing the time and resources for developing such an agent.…”

“…Furthermore only a few infectious agents are amenable to experimental approaches of gene essentiality, as the tools for identification of drug or vaccine targets are often limited or absent for many pathogens. In such scenarios, computational methods for gene essentiality prediction seem to streamline the gap between the amount of data generated from sequencing projects and whole genome approaches for prediction of essential genes (Agüero et al, 2008;Doyle et al, 2010;Volker and Brown, 2002).…”

Using Genomic Information to Understand Leishmania Biology

“…As mentioned above, there is a partnership between TriTrypDB and GeneDB teams and both Databases should be maintained and updated evenly to keep a similar content (personal communication on the EuPathDB WorkShop 2009). The availability of the complete DNA sequence of the human and human pathogens genomes [31,53] associated with the heavy expansion of information on chemical structures of known drugs and three-dimensional structures of potential new drug targets enables rational drug design [54][55][56]. Comparative genomic studies allow the identification of molecules or biochemical pathways that have already been targeted successfully in other pathogens [30,31].…”