RT Journal Article
SR Electronic
T1 Drug Target Ontology to Classify and Integrate Drug Discovery Data
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 117564
DO 10.1101/117564
A1 Yu Lin
A1 Saurabh Mehta
A1 Hande Küçük McGinty
A1 John Paul Turner
A1 Dusica Vidovic
A1 Michele Forlin
A1 Amar Koleti
A1 Dac-Trung Nguyen
A1 Lars Juhl Jensen
A1 Rajarshi Guha
A1 Stephen L. Mathias
A1 Oleg Ursu
A1 Vasileios Stathias
A1 Jianbin Duan
A1 Nooshin Nabizadeh
A1 Caty Chung
A1 Christopher Mader
A1 Ubbo Visser
A1 Jeremy J. Yang
A1 Cristian G. Bologa
A1 Tudor Oprea
A1 Stephan C. Schürer
YR 2017
UL http://biorxiv.org/content/early/2017/03/16/117564.abstract
AB 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.