@article{a7aad6eed20f44b49c9d1d1a72446c84,
title = "Unexplored therapeutic opportunities in the human genome",
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.",
author = "Oprea, {Tudor I.} and Bologa, {Cristian G.} and S{\o}ren Brunak and Allen Campbell and Gan, {Gregory N.} and Anna Gaulton and Gomez, {Shawn M.} and Rajarshi Guha and Anne Hersey and Jayme Holmes and Ajit Jadhav and Jensen, {Lars Juhl} and Johnson, {Gary L.} and Anneli Karlson and Leach, {Andrew R.} and Avi Ma'ayan and Anna Malovannaya and Subramani Mani and Mathias, {Stephen L.} and McManus, {Michael T.} and Meehan, {Terrence F.} and {Von Mering}, Christian and Daniel Muthas and Nguyen, {Dac Trung} and Overington, {John P.} and George Papadatos and Jun Qin and Christian Reich and Roth, {Bryan L.} and Sch{\"u}rer, {Stephan C.} and Anton Simeonov and Sklar, {Larry A.} and Noel Southall and Susumu Tomita and Ilinca Tudose and Oleg Ursu and Du{\v s}ica Vidovi{\'c} and Anna Waller and David Westergaard and Yang, {Jeremy J.} and Gergely Zahor{\'a}nszky-K{\"o}halmi",
note = "Funding Information: NIH R01 funding, 2011–2015 per target (US$) Funding Information: text-mining methods described earlier for FIG. 2. During the same period, 2011–2015, the NIH funded 42,924 R01 grant applications, at a total cost of $32 billion. These projects discuss up to 7,851 human proteins (see Supplementary Table S10). For example, R01 grants associated with oestrogen receptors were awarded $101 million, compared with $50 billion in sales earned by 18 drugs acting through oestrogen receptors during that same period (TABLE 2). Some targets, having over 30 drugs each, are also top-earning and well funded, for example, the μ-opioid (OPRM1) and the glucocorticoid (NR3C1) receptors. Other top-earning targets with over 30 drugs each, such as the β2 adrenergic receptor and cyclooxygenase 1, are not as well funded. We found no relationship between MIDAS global drug target sales and NIH R01 funding during the 2011–2015 period, even when factoring in the number of APIs per target. Overall, $4.2 billion was awarded to study 496 Tclin proteins, representing 13% of the R01 budget and 6% of all R01-funded proteins. Another 615 proteins (485 Tbio and 67 Tdark) had just one funded R01 project dedicated to their study during 2011–2015, and 8,857 proteins were not associated with any NIH funding for this time frame. AT1 receptor, angiotensin II type 1 receptor; COX2, cyclooxygenase 2; DPP4, dipeptidyl peptidase 4; HMG-CoA, 3-hydroxy-3-methylglutaryl-CoA. Publisher Copyright: {\textcopyright} 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.",
year = "2018",
month = apr,
day = "27",
doi = "10.1038/nrd.2018.14",
language = "English",
volume = "17",
pages = "317--332",
journal = "Nature Reviews Drug Discovery",
issn = "1474-1776",
publisher = "Nature Publishing Group",
number = "5",
}