TDR TARGETS: A CHEMOGENOMICS DATABASE FOR NEGLECTED DISEASES FOR DRUG REPURPOSING AND PROTEIN TARGET PRIORITIZATION

LANDABURU, LIONEL URÁN; DHANASEKARAN SHANMUGAM; CHERNOMORETZ, ARIEL; AGÜERO F

Buenos Aires

Simposio; XVIII Simposio Internacional sobre Enfermedades Desatendidas; 2017

Fundación Mundo Sano

TDR TARGETS: A CHEMOGENOMICS DATABASE FOR NEGLECTED DISEASES FOR DRUG REPURPOSING AND PROTEIN TARGET PRIORITIZATIONLionel Urán Landaburu1, Dhanasekaran Shanmugam2, Ariel Chernomoretz3, and Fernán Agüero11. Instituto de Investigaciones Biotecnológicas, UNSAM ? CONICET, San Martín, Buenos Aires, Argentina. 2. Biochemical Sciences Division, National Chemical Laboratory, Pune, Maharashtra, India3. Fundación Instituto Leloir, Buenos Aires, ArgentinaThe volume of biological and chemical data deposited in the public domain is growing fastly, thanks to next generation sequencing and screening technologies. Both academic research groups and big-pharma companies are contributing to this effort in the case of neglected tropical diseases. However, curated, functional and chemical information for most model organisms still vastly exceeds that for neglected diseases. In our laboratory, we have developed a chemogenomics database resource, TDR Targets (www.tdrtargets.org) [1] that aims to organize and integrate heterogeneous large datasets. The resource hosts both for genomic and chemical data with a focus on neglected diseases but also allows users to make use of information available for other organisms. The database facilitates target prioritizations by allowing users to formulate complex queries across diverse query spaces: biophysical properties (molecular weight, isoelectric point, etc), predicted annotations (Pfam domains, EC numbers, pathways, etc), as well as relevant functional data (essentiality, expression). Users may also search for bioactive compounds and their annotated targets and navigate the data by taking advantage of existing links (orthology to link targets, chemical similarity to link compounds) [2]. Compound searches can be done either by physicochemical features, by their bioactivities or assays or by drawing a molecules to look for similar compounds [2]. Here we present recent updates to the TDR Targets database resource. The database has been updated to integrate data on >2 million bioactive compounds from different sources; 19 pathogen genomes for WHO/TDR Targets; and 30 complete genomes for model organisms and other related pathogens. Available genomes include those of Trypanosomatids; Apicomplexans; Mycobateria; Metazoans (including flatworms and nematodes); Bacteria; other Early Branching Eukaryotes (Giardia, Trichomonas); and Amoebas (Entamoeba). We will also present advances in how users can explore drug-target relationships in a more intuitive manner, by taking advantage of chemogenomics data built into a novel network model [3].References: [1] Agüero F, Al-Lazikani B, Aslett M, et al. Genomic-scale prioritization of drug targets: the TDR Targets database (2008). Nature Reviews Drug Discovery 7: 900-907. [2] Magariños MP, Carmona SJ, Crowther GJ, et al. TDR Targets: a chemogenomics resource for neglected diseases (2012). Nucleic Acids Research 40: D1118-27. [3] A Multilayer Network Approach for Guiding Drug Repositioning in Neglected Diseases (2016). Berenstein AJ, Magariños MP, Chernomoretz A, Agüero F. PLOS Neglected Tropical Diseases 10: e0004300.Funding. Supported by CONICET and by grant PICTO-Glaxo-2013-0067 from the Agencia Nacional de Promoción Científica y Tecnológica, Argentina (ANPCyT).