Knowledge Management Center for Illuminating the Druggable Genome

Previous PI (Jan. 2018 - Jan. 2022)

Contacts

• Translational Informatics Division: http://datascience.unm.edu/
• TCRD (Target Central Resource Database): http://juniper.health.unm.edu/tcrd/
• REST API for TCRD (underlying data for Pharos): http://juniper.health.unm.edu/tcrd/api.html
• TINx (Target Importance and Novelty eXplorer):  http://newdrugtargets.org/
• DrugCentral (utilized to annotate Tclin): http://drugcentral.org/

Overview

KMC grant at UNM is led by Dr. Jeremy Edwards and includes collaborations with Dr. Lars Juhl Jensen’s lab at NNFCPR and at EMBL-EBI with Dr. Andrew Leach as their Group Lead. Work from UNM includes the development of TCRD, the main database supporting Pharos, and appropriate visualization tools, such as TINx. Work by this group include evaluation of the data collated into TCRD and led to the categorization of target proteins based on knowledge levels, Target Development Levels (TDL): Tdark are targets with least knowledge. Next level of development are Tbio, proteins with further annotation of function or biological process, including confirmed OMIM phenotypes. With the discovery of protein interacting with a drug or compound, these proteins are classified as Tchem if these compound activities satisfy activity thresholds set based on protein biological class. Further annotation via DrugCentral regarding the mechanism of action for approved drugs elevates the target into the TDL of Tclin, i.e., protein with highest attained annotation.

NIH grant number: 1U24 CA224370-01

Nature Rev. Drug Discov. Poster
Unexplored opportunities in the druggable human genome, T. Oprea, et al., Nature Rev. Drug Discov. Poster Jan. 2017.

KMC-UNM publications:

1. TCRD and Pharos 2021: mining the human proteome for disease biology. Sheils TK, Mathias SL, Kelleher KJ, Siramshetty VB, Nguyen DT, Bologa CG, Jensen LJ, Vidović D, Koleti A, Schürer SC, Waller A, Yang JJ, Holmes J, Bocci G, Southall N, Dharkar P, Mathé E, Simeonov A, Oprea TI. Nucleic Acids Res. 2020 Nov 6:gkaa993. doi: 10.1093/nar/gkaa993. Online ahead of print. PMID: 33156327


2. DrugCentral 2021 supports drug discovery and repositioning. Avram S, Bologa CG, Holmes J, Bocci G, Wilson TB, Nguyen DT, Curpan R, Halip L, Bora A, Yang JJ, Knockel J, Sirimulla S, Ursu O, Oprea TI. Nucleic Acids Res. 2020 Nov 5:gkaa997. doi: 10.1093/nar/gkaa997. Online ahead of print. PMID: 33151287


3. Artificial intelligence, drug repurposing and peer review. Levin JM, Oprea TI, Davidovich S, Clozel T, Overington JP, Vanhaelen Q, Cantor CR, Bischof E, Zhavoronkov A. Nat Biotechnol. 2020 Oct;38(10):1127-1131. doi: 10.1038/s41587-020-0686-x.PMID: 32929264


4. Off-Patent Drug Repositioning. Avram S, Curpan R, Halip L, Bora A, Oprea TI. J Chem Inf Model. 2020 Sep 15. doi: 10.1021/acs.jcim.0c00826. Online ahead of print. PMID: 32877182


5. Novel drug targets in 2019. Avram S, Halip L, Curpan R, Oprea TI. Nat Rev Drug Discov. 2020 May;19(5):300. doi: 10.1038/d41573-020-00052-w. PMID: 32273590


6. How many rare diseases are there? Haendel M, Vasilevsky N, Unni D, Bologa C, Harris N, Rehm H, Hamosh A, Baynam G, Groza T, McMurry J, Dawkins H, Rath A, Thaxon C, Bocci G, Joachimiak MP, Köhler S, Robinson PN, Mungall C, Oprea TI. Nat Rev Drug Discov. 2020 Feb;19(2):77-78. doi: 10.1038/d41573-019-00180-y. PMID: 32020066 No abstract available.


7. Will Artificial Intelligence for Drug Discovery Impact Clinical Pharmacology? Zhavoronkov A, Vanhaelen Q, Oprea TI. Clin Pharmacol Ther. 2020 Apr;107(4):780-785. doi: 10.1002/cpt.1795. Epub 2020 Mar 3. PMID: 31957003 Free PMC article. Review.


8. How to Illuminate the Druggable Genome Using Pharos. Sheils T, Mathias SL, Siramshetty VB, Bocci G, Bologa CG, Yang JJ, Waller A, Southall N, Nguyen DT, Oprea TI. Curr Protoc Bioinformatics. 2020 Mar;69(1):e92. doi: 10.1002/cpbi.92. PMID: 31898878


9. Can BDDCS illuminate targets in drug design? Bocci G, Benet LZ, Oprea TI. Drug Discov Today. 2019 Dec;24(12):2299-2306. doi: 10.1016/j.drudis.2019.09.021. Epub 2019 Oct 1. PMID: 31585170 Review.


10. Exploring the dark genome: implications for precision medicine. Oprea TI. Mamm Genome. 2019 Aug;30(7-8):192-200. doi: 10.1007/s00335-019-09809-0. Epub 2019 Jul 4. PMID: 31270560


11. The human endogenous metabolome as a pharmacology baseline for drug discovery. Bofill A, Jalencas X, Oprea TI, Mestres J. Drug Discov Today. 2019 Sep;24(9):1806-1820. doi: 10.1016/j.drudis.2019.06.007. Epub 2019 Jun 19. PMID: 31226432


12. How to Prepare a Compound Collection Prior to Virtual Screening. Bologa CG, Ursu O, Oprea TI. Methods Mol Biol. 2019;1939:119-138. doi: 10.1007/978-1-4939-9089-4_7. PMID: 30848459


13. How to Develop a Drug Target Ontology: Knowledge Acquisition and Representation Methodology (KNARM). Küçük McGinty H, Visser U, Schürer S. Methods Mol Biol. 2019;1939:49-69. doi: 10.1007/978-1-4939-9089-4_4. PMID: 30848456


14. DrugCentral 2018: an update. Ursu O, Holmes J, Bologa CG, Yang JJ, Mathias SL, Stathias V, Nguyen DT, Schürer S, Oprea T. Nucleic Acids Res. 2019 Jan 8;47(D1):D963-D970. doi: 10.1093/nar/gky963. PMID: 30371892


15. Darkness in the Human Gene and Protein Function Space: Widely Modest or Absent Illumination by the Life Science Literature and the Trend for Fewer Protein Function Discoveries Since 2000. Sinha S, Eisenhaber B, Jensen LJ, Kalbuaji B, Eisenhaber F. Proteomics. 2018 Nov;18(21-22):e1800093. doi: 10.1002/pmic.201800093. Epub 2018 Oct 30. PMID: 30265449


16. Proteomic analysis defines kinase taxonomies specific for subtypes of breast cancer. Collins KAL, Stuhlmiller TJ, Zawistowski JS, East MP, Pham TT, Hall CR, Goulet DR, Bevill SM, Angus SP, Velarde SH, Sciaky N, Oprea TI, Graves LM, Johnson GL, Gomez SM. Oncotarget. 2018 Jan 29;9(21):15480-15497. doi: 10.18632/oncotarget.24337. eCollection 2018 Mar 20. PMID: 29643987


17. Unexplored therapeutic opportunities in the human genome. 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 DT, 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. Nat Rev Drug Discov. 2018 May;17(5):317-332. doi: 10.1038/nrd.2018.14. Epub 2018 Mar 23. PMID: 29472638


18. Pharos: Collating protein information to shed light on the druggable genome. Nguyen DT, Mathias S, Bologa C, Brunak S, Fernandez N, Gaulton A, Hersey A, Holmes J, Jensen LJ, Karlsson A, Liu G, Ma'ayan A, Mandava G, Mani S, Mehta S, Overington J, Patel J, Rouillard AD, Schürer S, Sheils T, Simeonov A, Sklar LA, Southall N, Ursu O, Vidovic D, Waller A, Yang J, Jadhav A, Oprea TI, Guha R. Nucleic Acids Res. 2017 Jan 4;45(D1):D995-D1002. doi: 10.1093/nar/gkw1072. Epub 2016 Nov 29. PMID: 27903890, PMCID: PMC5210555


19. Unexplored opportunities in the druggable human genome, T. Oprea, et al., Nature Rev. Drug Discov. Poster Jan. 2017.