Unexplored therapeutic opportunities in the human genome

Tudor I Oprea; Cristian G Bologa; Søren Brunak; Allen Campbell; Gregory N Gan; Anna Gaulton; Shawn M Gomez; Rajarshi Guha; Anne Hersey; Jayme Holmes; Ajit Jadhav; Lars Juhl Jensen; Gary L Johnson; Anneli Karlson; Andrew R Leach; Avi Ma'ayan; Anna Malovannaya; Subramani Mani; Stephen L Mathias; Michael T McManus; Terrence F Meehan; Christian von Mering; Daniel Muthas; Dac-Trung Nguyen; John P Overington; George Papadatos; Jun Qin; Christian Reich; Bryan L Roth; Stephan C Schürer; Anton Simeonov; Larry A Sklar; Noel Southall; Susumu Tomita; Ilinca Tudose; Oleg Ursu; Dušica Vidovic; Anna Waller; David Westergaard; Jeremy J Yang; Gergely Zahoránszky-Köhalmi

doi:10.1038/nrd.2018.14

Unexplored therapeutic opportunities in the human genome

Tudor I Oprea, Cristian G Bologa, Søren Brunak, Allen Campbell, Gregory N Gan, Anna Gaulton, Shawn M Gomez, Rajarshi Guha, Anne Hersey, Jayme Holmes, Ajit Jadhav, Lars Juhl Jensen, Gary L Johnson, Anneli Karlson, Andrew R Leach, Avi Ma'ayan, Anna Malovannaya, Subramani Mani, Stephen L Mathias, Michael T McManusTerrence F Meehan, Christian von Mering, Daniel Muthas, Dac-Trung Nguyen, John P Overington, George Papadatos, Jun Qin, Christian Reich, Bryan L Roth, Stephan C Schürer, Anton Simeonov, Larry A Sklar, Noel Southall, Susumu Tomita, Ilinca Tudose, Oleg Ursu, Dušica Vidovic, Anna Waller, David Westergaard, Jeremy J Yang, Gergely Zahoránszky-Köhalmi

108 Citationer (Scopus)

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 two out of five 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.

Originalsprog	Engelsk
Tidsskrift	Nature Reviews. Drug Discovery
Vol/bind	17
Udgave nummer	5
Sider (fra-til)	317-332
Antal sider	16
ISSN	1474-1776
DOI	https://doi.org/10.1038/nrd.2018.14
Status	Udgivet - 2018

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Oprea, T. I., Bologa, C. G., Brunak, S., Campbell, A., Gan, G. N., Gaulton, A., Gomez, S. M., Guha, R., Hersey, A., Holmes, J., Jadhav, A., Jensen, L. J., Johnson, G. L., Karlson, A., Leach, A. R., Ma'ayan, A., Malovannaya, A., Mani, S., Mathias, S. L., ... Zahoránszky-Köhalmi, G. (2018). Unexplored therapeutic opportunities in the human genome. Nature Reviews. Drug Discovery, 17(5), 317-332. https://doi.org/10.1038/nrd.2018.14

Oprea, TI, Bologa, CG, Brunak, S, Campbell, A, Gan, GN, Gaulton, A, Gomez, SM, Guha, R, Hersey, A, Holmes, J, Jadhav, A, Jensen, LJ, Johnson, GL, Karlson, A, Leach, AR, Ma'ayan, A, Malovannaya, A, Mani, S, Mathias, SL, McManus, MT, Meehan, TF, von Mering, C, Muthas, D, Nguyen, D-T, Overington, JP, Papadatos, G, Qin, J, Reich, C, Roth, BL, Schürer, SC, Simeonov, A, Sklar, LA, Southall, N, Tomita, S, Tudose, I, Ursu, O, Vidovic, D, Waller, A, Westergaard, D, Yang, JJ & Zahoránszky-Köhalmi, G 2018, 'Unexplored therapeutic opportunities in the human genome', Nature Reviews. Drug Discovery, bind 17, nr. 5, s. 317-332. https://doi.org/10.1038/nrd.2018.14

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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 two out of five 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.",

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AU - Gaulton, Anna

AU - Gomez, Shawn M

AU - Guha, Rajarshi

AU - Hersey, Anne

AU - Holmes, Jayme

AU - Jadhav, Ajit

AU - Jensen, Lars Juhl

AU - Johnson, Gary L

AU - Karlson, Anneli

AU - Leach, Andrew R

AU - Ma'ayan, Avi

AU - Malovannaya, Anna

AU - Mani, Subramani

AU - Mathias, Stephen L

AU - McManus, Michael T

AU - Meehan, Terrence F

AU - von Mering, Christian

AU - Muthas, Daniel

AU - Nguyen, Dac-Trung

AU - Overington, John P

AU - Papadatos, George

AU - Qin, Jun

AU - Reich, Christian

AU - Roth, Bryan L

AU - Schürer, Stephan C

AU - Simeonov, Anton

AU - Sklar, Larry A

AU - Southall, Noel

AU - Tomita, Susumu

AU - Tudose, Ilinca

AU - Ursu, Oleg

AU - Vidovic, Dušica

AU - Waller, Anna

AU - Westergaard, David

AU - Yang, Jeremy J

AU - Zahoránszky-Köhalmi, Gergely

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AB - 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 two out of five 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.

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Unexplored therapeutic opportunities in the human genome

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