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Exploring the dark genome: implications for precision medicine

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Abstract

The increase in the number of both patients and healthcare practitioners who grew up using the Internet and computers (so-called “digital natives”) is likely to impact the practice of precision medicine, and requires novel platforms for data integration and mining, as well as contextualized information retrieval. The “Illuminating the Druggable Genome Knowledge Management Center” (IDG KMC) quantifies data availability from a wide range of chemical, biological, and clinical resources, and has developed platforms that can be used to navigate understudied proteins (the “dark genome”), and their potential contribution to specific pathologies. Using the “Target Importance and Novelty Explorer” (TIN-X) highlights the role of LRRC10 (a dark gene) in dilated cardiomyopathy. Combining mouse and human phenotype data leads to increased strength of evidence, which is discussed for four additional dark genes: SLX4IP and its role in glucose metabolism, the role of HSF2BP in coronary artery disease, the involvement of ELFN1 in attention-deficit hyperactivity disorder and the role of VPS13D in mouse neural tube development and its confirmed role in childhood onset movement disorders. The workflow and tools described here are aimed at guiding further experimental research, particularly within the context of precision medicine.

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Acknowledgements

This work was supported by NIH Grants U54CA189205, U24CA224370 (for IDG KMC), and U24TR002278 (for IDG RDOC).

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Authors and Affiliations

  1. Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM, USA

    Tudor I. Oprea

  2. UNM Comprehensive Cancer Center, Albuquerque, NM, USA

    Tudor I. Oprea

  3. Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

    Tudor I. Oprea

  4. Faculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark

    Tudor I. Oprea

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Correspondence to Tudor I. Oprea.

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Dr. Oprea was a former full-time employee at AstraZeneca (1996–2002). He has received honoraria, or consulted for, Abbott, AstraZeneca, Chiron, Genentech, Infinity Pharmaceuticals, Merz Pharmaceuticals, Merck Darmstadt, Mitsubishi Tanabe, Novartis, Ono Pharmaceuticals, Pfizer, Roche, Sanofi, and Wyeth. His spouse was a full-time employee of AstraZeneca (2002–2014) and is a full-time employee of Genentech Inc.

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Oprea, T.I. Exploring the dark genome: implications for precision medicine. Mamm Genome 30, 192–200 (2019). https://doi.org/10.1007/s00335-019-09809-0

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