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Drug target ontology to classify and integrate drug discovery data.

ABSTRACT: 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 developed 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 supporting manual knowledge acquisition. A modular, hierarchical implementation facilitate ontology 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 characteristics. 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 the website http://drugtargetontology.org/ , Github ( http://github.com/DrugTargetOntology/DTO ), and the NCBO Bioportal ( http://bioportal.bioontology.org/ontologies/DTO ). 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.

SUBMITTER: Lin Y

PROVIDER: S-EPMC5679337 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Drug target ontology to classify and integrate drug discovery data.

Lin Yu Y Mehta Saurabh S Küçük-McGinty Hande H Turner John Paul JP Vidovic Dusica D Forlin Michele M Koleti Amar A Nguyen Dac-Trung DT Jensen Lars Juhl LJ Guha Rajarshi R Mathias Stephen L SL Ursu Oleg O Stathias Vasileios V Duan Jianbin J Nabizadeh Nooshin N Chung Caty C Mader Christopher C Visser Ubbo U Yang Jeremy J JJ Bologa Cristian G CG Oprea Tudor I TI Schürer Stephan C SC

Journal of biomedical semantics 20171109 1

<h4>Background</h4>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 ...[more]

PMID: 29122012

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Project description:The process of discovering new drugs is a lengthy, time-consuming and expensive process. Modern day drug discovery relies heavily on the rapid identification of novel 'targets', usually proteins that can be modulated by small molecule drugs to cure or minimise the effects of a disease. Of the 20,000 proteins currently reported as comprising the human proteome, just under a quarter of these can potentially be modulated by known small molecules Storing information in curated, actively maintained drug discovery databases can help researchers access current drug discovery information quickly. However with the increase in the amount of data generated from both experimental and in silico efforts, databases can become very large very quickly and information retrieval from them can become a challenge. The development of database tools that facilitate rapid information retrieval is important to keep up with the growth of databases.We have developed a Gene Ontology-based navigation tool (Gene Ontology Tree) to help users retrieve biological information to single protein targets in the ChEMBL drug discovery database. 99 % of single protein targets in ChEMBL have at least one GO annotation associated with them. There are 12,500 GO terms associated to 6200 protein targets in the ChEMBL database resulting in a total of 140,000 annotations. The slim we have created, the 'ChEMBL protein target slim' allows broad categorisation of the biology of 90 % of the protein targets using just 300 high level, informative GO terms. We used the GO slim method of assigning fewer higher level GO groupings to numerous very specific lower level terms derived from the GOA to describe a set of GO terms relevant to proteins in ChEMBL. We then used the slim created to provide a web based tool that allows a quick and easy navigation of protein target space. Terms from the GO are used to capture information on protein molecular function, biological process and subcellular localisations. The ChEMBL database also provides compound information for small molecules that have been tested for their effects on these protein targets. The 'ChEMBL protein target slim' provides a means of firstly describing the biology of protein drug targets and secondly allows users to easily establish a connection between biological and chemical information regarding drugs and drug targets in ChEMBL. The 'ChEMBL protein target slim' is available as a browsable 'Gene Ontology Tree' on the ChEMBL site under the browse targets tab ( https://www.ebi.ac.uk/chembl/target/browser ). A ChEMBL protein target slim OBO file containing the GO slim terms pertinent to ChEMBL is available from the GOC website ( http://geneontology.org/page/go-slim-and-subset-guide ).We have created a protein target navigation tool based on the 'ChEMBL protein target slim'. The 'ChEMBL protein target slim' provides a way of browsing protein targets in ChEMBL using high level GO terms that describe the molecular functions, processes and subcellular localisations of protein drug targets in drug discovery. The tool also allows user to establish a link between ontological groupings representing protein target biology to relevant compound information in ChEMBL. We have demonstrated by the use of a simple example how the 'ChEMBL protein target slim' can be used to link biological processes with drug information based on the information in the ChEMBL database. The tool has potential to aid in areas of drug discovery such as drug repurposing studies or drug-disease-protein pathways.

Project description:BackgroundWeb-based resources and social media platforms play an increasingly important role in health-related knowledge and experience sharing. There is a growing interest in the use of these novel data sources for epidemiological surveillance of substance use behaviors and trends.ObjectiveThe key aims were to describe the development and application of the drug abuse ontology (DAO) as a framework for analyzing web-based and social media data to inform public health and substance use research in the following areas: determining user knowledge, attitudes, and behaviors related to nonmedical use of buprenorphine and illicitly manufactured opioids through the analysis of web forum data Prescription Drug Abuse Online Surveillance; analyzing patterns and trends of cannabis product use in the context of evolving cannabis legalization policies in the United States through analysis of Twitter and web forum data (eDrugTrends); assessing trends in the availability of novel synthetic opioids through the analysis of cryptomarket data (eDarkTrends); and analyzing COVID-19 pandemic trends in social media data related to 13 states in the United States as per Mental Health America reports.MethodsThe domain and scope of the DAO were defined using competency questions from popular ontology methodology (101 ontology development). The 101 method includes determining the domain and scope of ontology, reusing existing knowledge, enumerating important terms in ontology, defining the classes, their properties and creating instances of the classes. The quality of the ontology was evaluated using a set of tools and best practices recognized by the semantic web community and the artificial intelligence community that engage in natural language processing.ResultsThe current version of the DAO comprises 315 classes, 31 relationships, and 814 instances among the classes. The ontology is flexible and can easily accommodate new concepts. The integration of the ontology with machine learning algorithms dramatically decreased the false alarm rate by adding external knowledge to the machine learning process. The ontology is recurrently updated to capture evolving concepts in different contexts and applied to analyze data related to social media and dark web marketplaces.ConclusionsThe DAO provides a powerful framework and a useful resource that can be expanded and adapted to a wide range of substance use and mental health domains to help advance big data analytics of web-based data for substance use epidemiology research.

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Drug target ontology to classify and integrate drug discovery data.

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Drug target ontology to classify and integrate drug discovery data.

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