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Nat Rev Drug Discov. 2018 May;17(5):317-332. doi: 10.1038/nrd.2018.14. Epub 2018 Mar 23.

Unexplored therapeutic opportunities in the human genome.

Author information

1
Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM, USA.
2
UNM Comprehensive Cancer Center, Albuquerque, NM, USA.
3
Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
4
Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
5
IQVIA, Plymouth Meeting, PA, USA.
6
European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridge, UK.
7
Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, NC, USA.
8
Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
9
National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH), Rockville, MD, USA.
10
SciBite Limited, BioData Innovation Centre, Wellcome Genome Campus, Hinxton, Cambridge, UK.
11
Icahn School of Medicine at Mount Sinai, New York, NY, USA.
12
Baylor College of Medicine, Houston, TX, USA.
13
University of California, San Francisco, CA, USA.
14
Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
15
Respiratory, Inflammation and Autoimmunity Diseases, Innovative Medicines and Early Development Biotech Unit, AstraZeneca R&D Gothenburg, Mölndal, Sweden.
16
Medicines Discovery Catapult, Alderley Edge, UK.
17
GlaxoSmithKline, Stevenage, UK.
18
IQVIA, Cambridge, MA, USA.
19
Department of Molecular and Cellular Pharmacology, Miller School of Medicine, University of Miami, Miami, FL, USA.
20
Center for Molecular Discovery, University of New Mexico Cancer Center, University of New Mexico, Albuquerque, NM, USA.
21
Department of Pathology, University of New Mexico, Albuquerque, NM, USA.
22
Yale School of Medicine, Yale University, New Haven, CT, USA.
23
Google Germany GmbH, München, Germany.
24
NIH-NCATS, Rockville, MD, USA.

Erratum in

Abstract

A large proportion of biomedical research and the development of therapeutics is focused on a small fraction of the human genome. In a strategic effort to map the knowledge gaps around proteins encoded by the human genome and to promote the exploration of currently understudied, but potentially druggable, proteins, the US National Institutes of Health launched the Illuminating the Druggable Genome (IDG) initiative in 2014. In this article, we discuss how the systematic collection and processing of a wide array of genomic, proteomic, chemical and disease-related resource data by the IDG Knowledge Management Center have enabled the development of evidence-based criteria for tracking the target development level (TDL) of human proteins, which indicates a substantial knowledge deficit for approximately one out of three proteins in the human proteome. We then present spotlights on the TDL categories as well as key drug target classes, including G protein-coupled receptors, protein kinases and ion channels, which illustrate the nature of the unexplored opportunities for biomedical research and therapeutic development.

PMID:
29472638
DOI:
10.1038/nrd.2018.14

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