TY - JOUR T1 - Drug Target Ontology to Classify and Integrate Drug Discovery Data JF - bioRxiv DO - 10.1101/117564 SP - 117564 AU - Yu Lin AU - Saurabh Mehta AU - Hande Küçük McGinty AU - John Paul Turner AU - Dusica Vidovic AU - Michele Forlin AU - Amar Koleti AU - Dac-Trung Nguyen AU - Lars Juhl Jensen AU - Rajarshi Guha AU - Stephen L. Mathias AU - Oleg Ursu AU - Vasileios Stathias AU - Jianbin Duan AU - Nooshin Nabizadeh AU - Caty Chung AU - Christopher Mader AU - Ubbo Visser AU - Jeremy J. Yang AU - Cristian G. Bologa AU - Tudor Oprea AU - Stephan C. Schürer Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/03/16/117564.abstract N2 - Background One of the most successful approaches to develop new small molecule therapeutics has been to start from a validated druggable protein target. However, only a small subset of potentially druggable targets has attracted significant research and development resources. The Illuminating the Druggable Genome (IDG) project develops resources to catalyze the development of likely targetable, yet currently understudied prospective drug targets. A central component of the IDG program is a comprehensive knowledge resource of the druggable genome.Results As part of that effort, we have been developing a framework to integrate, navigate, and analyze drug discovery data based on formalized and standardized classifications and annotations of druggable protein targets, the Drug Target Ontology (DTO). DTO was constructed by extensive curation and consolidation of various resources. DTO classifies the four major drug target protein families, GPCRs, kinases, ion channels and nuclear receptors, based on phylogenecity, function, target development level, disease association, tissue expression, chemical ligand and substrate characteristics, and target-family specific characteristics. The formal ontology was built using a new software tool to auto-generate most axioms from a database while also supporting manual knowledge acquisition. A modular, hierarchical implementation facilitates development and maintenance and makes use of various external ontologies, thus integrating the DTO into the ecosystem of biomedical ontologies. As a formal OWL-DL ontology, DTO contains asserted and inferred axioms. Modeling data from the Library of Integrated Network-based Cellular Signatures (LINCS) program illustrates the potential of DTO for contextual data integration and nuanced definition of important drug target data. DTO has been implemented in the IDG user interface Portal, Pharos and the TIN-X explorer of protein target disease relationships.Conclusions DTO was built based on the need for a formal semantic model for druggable targets including various related information such as protein, gene, protein domain, protein structure, binding site, small molecule drug, mechanism of action, protein tissue localization, disease association, and many other types of information. DTO will further facilitate the otherwise challenging integration and formal linking to biological assays, phenotypes, disease models, drug poly-pharmacology, binding kinetics and many other processes, functions and qualities that are at the core of drug discovery. The first version of DTO is publically available via several mechanisms. The long-term goal of DTO is to provide such an integrative framework and to populate the ontology with this information as a community resource. ER -