Starting with the launch of the Human Genome Project three decades ago, and continuing after its completion in 2003, genomics has progressively come to have a central and catalytic role in basic and translational research. In addition, studies increasingly demonstrate how genomic information can be effectively used in clinical care. In the future, the anticipated advances in technology development, biological insights, and clinical applications (among others) will lead to more widespread integration of genomics into almost all areas of biomedical research, the adoption of genomics into mainstream medical and public-health practices, and an increasing relevance of genomics for everyday life. On behalf of the research community, the National Human Genome Research Institute recently completed a multi-year process of strategic engagement to identify future research priorities and opportunities in human genomics, with an emphasis on health applications. Here we describe the highest-priority elements envisioned for the cutting-edge of human genomics going forward—that is, at ‘The Forefront of Genomics’.
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The Human Genome Project; https://www.genome.gov/human-genome-project (accessed 28 June 2020)
Lander, E. S. et al. Initial sequencing and analysis of the human genome. Nature 409, 860–921 (2001).
International Human Genome Sequencing Consortium. Finishing the euchromatic sequence of the human genome. Nature 431, 931–945 (2004).
NHGRI. The cost of sequencing a human genome; https://www.genome.gov/about-genomics/fact-sheets/Sequencing-Human-Genome-cost (accessed 12 June 2020)
Moore, J. E. et al. Expanded encyclopaedias of DNA elements in the human and mouse genomes. Nature 583, 699–710 (2020).
Shema, E., Bernstein, B. E. & Buenrostro, J. D. Single-cell and single-molecule epigenomics to uncover genome regulation at unprecedented resolution. Nat. Genet. 51, 19–25 (2019).
The 1000 Genomes Project Consortium et al. A global reference for human genetic variation. Nature 526, 68–74 (2015).
Karczewski, K. J. et al. The mutational constraint spectrum quantified from variation in 141,456 humans. Nature 581, 434–443 (2020). Analysis of a large dataset of exome sequences, yielding important descriptions of the extent and nature of human genomic variation and insights into protein evolution.
Posey, J. E. et al. Insights into genetics, human biology and disease gleaned from family based genomic studies. Genet. Med. 21, 798–812 (2019).
Claussnitzer, M. et al. A brief history of human disease genetics. Nature 577, 179–189 (2020).
Manolio, T. A. et al. Opportunities, resources, and techniques for implementing genomics in clinical care. Lancet 394, 511–520 (2019).
Mardis, E. R. The impact of next-generation sequencing on cancer genomics: from discovery to clinic. Cold Spring Harb. Perspect. Med. 9, a036269 (2019).
Bianchi, D. W. & Chiu, R. W. K. Sequencing of circulating cell-free DNA during pregnancy. N. Engl. J. Med. 379, 464–473 (2018).
Wright, C. F., FitzPatrick, D. R. & Firth, H. V. Paediatric genomics: diagnosing rare disease in children. Nat. Rev. Genet. 19, 253–268 (2018).
Collins, F. S., Green, E. D., Guttmacher, A. E. & Guyer, M. S. A vision for the future of genomics research. Nature 422, 835–847 (2003).
Green, E. D. & Guyer, M. S. Charting a course for genomic medicine from base pairs to bedside. Nature 470, 204–213 (2011).
McEwen, J. E. et al. The Ethical, Legal, and Social Implications Program of the National Human Genome Research Institute: reflections on an ongoing experiment. Annu. Rev. Genomics Hum. Genet. 15, 481–505 (2014).
Burke, W. et al. The translational potential of research on the ethical, legal, and social implications of genomics. Genet. Med. 17, 1–9 (2014).
Popejoy, A. B. & Fullerton, S. M. Genomics is failing on diversity. Nature 538, 161–164 (2016). Comprehensive analysis of genome-wide association studies, demonstrating continued severe underrepresentation of individuals of African and Latin American ancestry and Indigenous peoples.
Wolf, S. M. et al. Integrating rules for genomic research, clinical care, public health screening and DTC testing: creating translational law for translational genomics. J. Law Med. Ethics 48, 69–86 (2020).
Adam, D. The promise and peril of the new science of social genomics. Nature 574, 618–620 (2019). Summary of recent studies examining the genetics of bio-behavioural traits, highlighting dangers to groups and society of over-interpreting results in this new field.
Dias, R. & Torkamani, A. Artificial intelligence in clinical and genomic diagnostics. Genome Med. 11, 70 (2019).
Schloss, J. A., Gibbs, R. A., Makhijani, V. B. & Marziali, A. Cultivating DNA sequencing technology after the human genome project. Annu. Rev. Genomics Hum. Genet. 21, 117–138 (2020). Retrospective overview of the NHGRI program for advancing DNA-sequencing technologies, the goal of which was to reduce the cost of sequencing a human genome to $1,000.
ENCODE: Encyclopedia of DNA Elements; https://www.encodeproject.org/ (accessed 24 June 2020).
Risca, V. I. & Greenleaf, W. J. Unraveling the 3D genome: genomics tools for multiscale exploration. Trends Genet. 31, 357–372 (2015).
Logsdon, G. A., Vollger, M. R. & Eichler, E. E. Long-read human genome sequencing and its applications. Nat. Rev. Genet. https://doi.org/10.1038/s41576-020-0236-x (2020).
Miga, K. H. et al. Telomere-to-telomere assembly of a complete human X chromosome. Nature 585, 79–84 (2020). Demonstration of the use of emerging DNA-sequencing technologies, analysis methods, and validation routines to produce the first gapless de novo assembly of a human chromosome sequence.
Human Pangenome Reference Consortium. Diverse human references drive genomic discoveries for everyone; https://humanpangenome.org/ (accessed 29 June 2020)
Zerbino, D. R., Frankish, A. & Flicek, P. Progress, challenges, and surprises in annotating the human genome. Annu. Rev. Genomics Hum. Genet. 21, 55–79 (2020).
Rood, J. E. et al. Toward a common coordinate framework for the human body. Cell 179, 1455–1467 (2019).
Stuart, T. & Satija, R. Integrative single-cell analysis. Nat. Rev. Genet. 20, 257–272 (2019).
Mimitou, E. P. et al. Multiplexed detection of proteins, transcriptomes, clonotypes and CRISPR perturbations in single cells. Nat. Methods 16, 409–412 (2019).
Schreiber, J., Durham, T., Bilmes, J. & Noble, W. S. Avocado: a multi-scale deep tensor factorization method learns a latent representation of the human epigenome. Genome Biol. 21, 81 (2020).
Cunningham, F. et al. Ensembl 2019. Nucleic Acids Res. 47 (D1), D745–D751 (2019).
Lewin, H. A. et al. Earth BioGenome Project: Sequencing life for the future of life. Proc. Natl Acad. Sci. USA 115, 4325–4333 (2018).
Lindblad-Toh, K. What animals can teach us about evolution, the human genome, and human disease. Ups. J. Med. Sci. 125, 1–9 (2020).
Schatz, M. C. Biological data sciences in genome research. Genome Res. 25, 1417–1422 (2015).
Wilkinson, M. D. et al. The FAIR Guiding Principles for scientific data management and stewardship. Sci. Data 3, 160018 (2016). Description of foundational principles to improve data sharing and stewardship by ensuring that biomedical research data (including genomic data) are findable, accessible, interoperable, and reusable.
Anderson, W. et al. Towards coordinated international support of core data resources for the life sciences. Preprint at https://www.bioRxiv.org/content/10.1101/110825v3 (2017).
Grossman, R. L. Data lakes, clouds, and commons: a review of platforms for analyzing and sharing genomic data. Trends Genet. 35, 223–234 (2019).
Haendel, M. A., Chute, C. G. & Robinson, P. N. Classification, ontology, and precision medicine. N. Engl. J. Med. 379, 1452–1462 (2018).
Martínez-Romero, M. et al. Using association rule mining and ontologies to generate metadata recommendations from multiple biomedical databases. Database (Oxford) 2019, 59 (2019).
Levy, K. D. et al. Opportunities to implement a sustainable genomic medicine program: lessons learned from the IGNITE Network. Genet. Med. 21, 743–747 (2019).
Williams, M. S. et al. Genomic information for clinicians in the electronic health record: Lessons learned from the clinical genome resource project and the electronic medical records and genomics network. Front. Genet. 10, 1059 (2019).
Lemke, A. A. et al. Primary care physician experiences utilizing a family health history tool with electronic health record-integrated clinical decision support: an implementation process assessment. J. Community Genet. 11, 339–350 (2020).
Khera, A. V. et al. Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations. Nat. Genet. 50, 1219–1224 (2018). Development and validation of genome-wide polygenic scores that identify population subsets with risk levels equivalent to monogenic genomic variants that are commonly reported and acted upon.
Zeggini, E., Gloyn, A. L., Barton, A. C. & Wain, L. V. Translational genomics and precision medicine: Moving from the lab to the clinic. Science 365, 1409–1413 (2019).
Koehly, L. M. et al. Social and behavioral science at the forefront of genomics: discovery, translation, and health equity. Soc. Sci. Med. 112450, 112450 (2019).
Khan, S. S., Cooper, R. & Greenland, P. Do polygenic risk scores improve patient selection for prevention of coronary artery disease? J. Am. Med. Assoc. 323, 614–615 (2020).
Mostafavi, H. et al. Variable prediction accuracy of polygenic scores within an ancestry group. eLife 9, 1–52 (2020).
Morris, T. T., Davies, N. M., Hemani, G. & Smith, G. D. Population phenomena inflate genetic associations of complex social traits. Sci. Adv. 6, eaay0328 (2020).
Bycroft, C. et al. The UK Biobank resource with deep phenotyping and genomic data. Nature 562, 203–209 (2018).
Denny, J. C. et al. The “All of Us” Research Program. N. Engl. J. Med. 381, 668–676 (2019).
Garrison, N. A. et al. Genomic research through an indigenous lens: understanding the expectations. Annu. Rev. Genomics Hum. Genet. 20, 495–517 (2019). Discussion of issues related to conducting genomics research with Indigenous peoples, coupled with suggestions for respecting tribal governance and protecting Indigenous people from group harms.
Sanderson, S. C. et al. Public attitudes toward consent and data sharing in biobank research: a large multi-site experimental survey in the US. Am. J. Hum. Genet. 100, 414–427 (2017). Survey results from 13,000 individuals regarding participation in research in which their data are shared with others, yielding insight into factors that predict a willingness of people to participate in research and concerns about data privacy.
Milne, R. et al. Trust in genomic data sharing among members of the general public in the UK, USA, Canada and Australia. Hum. Genet. 138, 1237–1246 (2019).
Grishin, D., Obbad, K. & Church, G. M. Data privacy in the age of personal genomics. Nat. Biotechnol. 37, 1115–1117 (2019).
Genomic Literacy, Education and Engagement Initiative; https://www.genome.gov/leadership-initiatives/Genomic-Literacy-Education-Engagement-Initiative (accessed 29 June 2020)
Manolio, T. A. & Murray, M. F. The growing role of professional societies in educating clinicians in genomics. Genet. Med. 16, 571–572 (2014).
Krakow, M., Ratcliff, C. L., Hesse, B. W. & Greenberg-Worisek, A. J. Assessing genetic literacy awareness and knowledge gaps in the US population: results from the health information national trends survey. Public Health Genomics 20, 343–348 (2017).
LaRue, K. M., McKernan, M. P., Bass, K. M. & Wray, C. G. Teaching the genome generation: bringing modern human genetics into the classroom through teacher professional development. J. STEM Outreach 1, 48–60 (2018).
Mboowa, G. & Sserwadda, I. Role of genomics literacy in reducing the burden of common genetic diseases in Africa. Mol. Genet. Genomic Med. 7, e00776 (2019).
Veilleux, S., Bouffard, M. & Bourque Bouliane, M. Patient and health care provider needs and preferences in understanding pharmacogenomic and genomic testing: a meta-data analysis. Qual. Health Res. 30, 43–59 (2020).
Kung, J. & Wu, C.-T. Leveling the playing field: closing the gap in public awareness of genetics between the well served and underserved. Hastings Cent. Rep. 46, 17–20 (2016).
Stephens, Z. D. et al. Big data: astronomical or genomical? PLoS Biol. 13, e1002195 (2015).
Attwood, T. K., Blackford, S., Brazas, M. D., Davies, A. & Schneider, M. V. A global perspective on evolving bioinformatics and data science training needs. Brief. Bioinform. 20, 398–404 (2019).
Genomics Education Partnership; http://gep.wustl.edu/ (accessed 16 June 2020).
Campion, M., Goldgar, C., Hopkin, R. J., Prows, C. A. & Dasgupta, S. Genomic education for the next generation of health-care providers. Genet. Med. 21, 2422–2430 (2019).
McClaren, B. J. et al. Development of an evidence-based, theory-informed national survey of physician preparedness for genomic medicine and preferences for genomics continuing education. Front. Genet. 11, 59 (2020).
Dougherty, M. J., Wicklund, C. & Johansen Taber, K. A. Challenges and opportunities for genomics education: Insights from an Institute of Medicine Roundtable Activity. J. Contin. Educ. Health Prof. 36, 82–85 (2016).
NHGRI. Inter-Society Coordinating Committee for Practitioner Education in Genomics; https://www.genome.gov/For-Health-Professionals/Inter-Society-Coordinating-Committee-for-Practitioner-Education-in-Genomics (accessed 16 June 2020).
Valantine, H. A., Collins, F. S. & Verma, I. M. National Institutes of Health addresses the science of diversity. Proc. Natl Acad. Sci. USA 112, 12240–12242 (2015).
Hofstra, B. et al. The diversity–innovation paradox in science. Proc. Natl Acad. Sci. USA 117, 9284–9291 (2020). Study of the US doctorate recipients from 1977 to 2015, identifying new contributions by gender and racial or ethnic minority scholars, evidence for lower rates of recognition by majority scholars, and the resulting diversity–innovation paradox in science.
Martinez, L. R., Boucaud, D. W., Casadevall, A. & August, A. Factors contributing to the success of NIH-designated underrepresented minorities in academic and nonacademic research positions. CBE Life Sci. Educ. 17, ar32 (2018).
Schindler, D., Dai, J. & Cai, Y. Synthetic genomics: a new venture to dissect genome fundamentals and engineer new functions. Curr. Opin. Chem. Biol. 46, 56–62 (2018).
Doudna, J. A. The promise and challenge of therapeutic genome editing. Nature 578, 229–236 (2020). Review of the scientific, technical, and ethical aspects of using CRISPR technology for therapeutic applications in humans.
UK Biobank; https://www.ukbiobank.ac.uk/ (accessed 14 June 2020).
NIH. All of Us; https://allofus.nih.gov/ (accessed 14 June 2020).
International HundredK+ Cohorts Consortium (IHCC). Linking cohorts, understanding biology, improving health; https://ihccglobal.org/ (accessed 14 June 2020).
Birney, E., Vamathevan, J. & Goodhand, P. Genomics in healthcare: GA4GH looks to 2022. Preprint at https://www.bioRxiv.org/content/10.1101/203554v1 (2017).
Stark, Z. et al. Integrating genomics into healthcare: a global responsibility. Am. J. Hum. Genet. 104, 13–20 (2019).
Manolio, T. A. et al. Bedside back to bench: building bridges between basic and clinical genomic research. Cell 169, 6–12 (2017).
Rehm, H. L. et al. ClinGen — The clinical genome resource. N. Engl. J. Med. 372, 2235–2242 (2015).
Starita, L. M. et al. Variant interpretation: functional assays to the rescue. Am. J. Hum. Genet. 101, 315–325 (2017).
International Common Disease Alliance; https://www.icda.bio/ (accessed 24 June 2020).
Welcome to the Pan-Cancer Atlas; https://www.cell.com/pb-assets/consortium/PanCancerAtlas/PanCani3/index.html (accessed 19 June 2020).
Steensma, D. P. et al. Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes. Blood 126, 9–16 (2015).
Baslan, T. & Hicks, J. Unravelling biology and shifting paradigms in cancer with single-cell sequencing. Nat. Rev. Cancer 17, 557–569 (2017).
D’Gama, A. M. & Walsh, C. A. Somatic mosaicism and neurodevelopmental disease. Nat. Neurosci. 21, 1504–1514 (2018).
Roden, D. M. et al. Pharmacogenomics. Lancet 394, 521–532 (2019).
Corbin, L. J. et al. Formalising recall by genotype as an efficient approach to detailed phenotyping and causal inference. Nat. Commun. 9, 711 (2018).
Savatt, J. M. et al. ClinGen’s GenomeConnect registry enables patient-centered data sharing. Hum. Mutat. 39, 1668–1676 (2018).
Eadon, M. T. et al. Implementation of a pharmacogenomics consult service to support the INGENIOUS trial. Clin. Pharmacol. Ther. 100, 63–66 (2016).
Darnell, A. J. et al. A clinical service to support the return of secondary genomic findings in human research. Am. J. Hum. Genet. 98, 435–441 (2016).
CDC. Public Health Genomics and Precision Health Knowledge Base (v6.4); https://phgkb.cdc.gov/PHGKB/tierStartPage.action (accessed 17 June 2020).
Dotson, W. D. et al. Prioritizing genomic applications for action by level of evidence: a horizon-scanning method. Clin. Pharmacol. Ther. 95, 394–402 (2014).
Hopkins, P. N. Genotype-guided diagnosis in familial hypercholesterolemia: population burden and cascade screening. Curr. Opin. Lipidol. 28, 136–143 (2017).
Bierne, H., Hamon, M. & Cossart, P. Epigenetics and bacterial infections. Cold Spring Harb. Perspect. Med. 2, a010272 (2012).
Bhat, A. A. et al. Role of non-coding RNA networks in leukemia progression, metastasis and drug resistance. Mol. Cancer 19, 57 (2020).
Sparks, T. M., Harabula, I. & Pombo, A. Evolving methodologies and concepts in 4D nucleome research. Curr. Opin. Cell Biol. 64, 105–111 (2020).
Young, A. I., Benonisdottir, S., Przeworski, M. & Kong, A. Deconstructing the sources of genotype-phenotype associations in humans. Science 365, 1396–1400 (2019).
Mitra, K., Carvunis, A.-R., Ramesh, S. K. & Ideker, T. Integrative approaches for finding modular structure in biological networks. Nat. Rev. Genet. 14, 719–732 (2013).
Bien, S. A. et al. The future of genomic studies must be globally representative: perspectives from PAGE. Annu. Rev. Genomics Hum. Genet. 20, 181–200 (2019).
Bentley, A. R., Callier, S. L. & Rotimi, C. N. Evaluating the promise of inclusion of African ancestry populations in genomics. Genomic Med. 5, 5 (2020).
Hindorff, L. A. et al. Prioritizing diversity in human genomics research. Nat. Rev. Genet. 19, 175–185 (2018).
Wojcik, G. L. et al. Genetic analyses of diverse populations improves discovery for complex traits. Nature 570, 514–518 (2019).
Landry, L. G., Ali, N., Williams, D. R., Rehm, H. L. & Bonham, V. L. Lack of diversity in genomic databases is a barrier to translating precision medicine research into practice. Health Aff. (Millwood) 37, 780–785 (2018).
Manrai, A. K. et al. Genetic misdiagnoses and the potential for health disparities. N. Engl. J. Med. 375, 655–665 (2016). Demonstration of frequent erroneous classification of genomic variants as pathogenic among patients of African or unspecified ancestry that were subsequently re-categorized as benign, with considerable health implications of those misclassifications.
Martin, A. R. et al. Clinical use of current polygenic risk scores may exacerbate health disparities. Nat. Genet. 51, 584–591 (2019).
Horowitz, C. R. et al. Successful recruitment and retention of diverse participants in a genomics clinical trial: a good invitation to a great party. Genet. Med. 21, 2364–2370 (2019).
Botkin, J. R., Mancher, M., Busta, E. R. & Downey, A. S. Returning Individual Research Results to Participants (National Academies Press, 2018).
Lázaro-Muñoz, G. et al. Issues facing us. Am. J. Med. Genet. B. Neuropsychiatr. Genet. 180, 543–554 (2019).
Lloyd-Price, J. et al. Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases. Nature 569, 655–662 (2019).
Hasin, Y., Seldin, M. & Lusis, A. Multi-omics approaches to disease. Genome Biol. 18, 83 (2017).
Chambers, D. A., Feero, W. G. & Khoury, M. J. Convergence of implementation science, precision medicine, and the learning health care system: a new model for biomedical research. J. Am. Med. Assoc. 315, 1941–1942 (2016).
Sugano, S. International code of conduct for genomic and health-related data sharing. HUGO J. 8, 1 (2014).
Clayton, E. W., Halverson, C. M., Sathe, N. A. & Malin, B. A. A systematic literature review of individuals’ perspectives on privacy and genetic information in the United States. PLoS One 13, e0204417 (2018).
Cavallari, L. H. et al. Multi-site investigation of strategies for the clinical implementation of CYP2D6 genotyping to guide drug prescribing. Genet. Med. 21, 2255–2263 (2019).
Ginsburg, G. S. A global collaborative to advance genomic medicine. Am. J. Hum. Genet. 104, 407–409 (2019).
The strategic vision described here was formulated on behalf of the NHGRI. We are grateful to the many members of the institute staff for their contributions to the associated planning process (see http://genome.gov/genomics2020 for details) as well as to the numerous external colleagues who provided input to the process and draft versions of this strategic vision. The National Advisory Council for Human Genome Research (current members are J. Botkin, T. Ideker, S. Plon, J. Haines, S. Fodor, R. Irizarry, P. Deverka, W. Chung, M. Craven, H. Dietz, S. Rich, H. Chang, L. Parker, L. Pennacchio, and O. Troyanskaya) ratified the strategic planning process, themes, and priorities associated with this strategic vision.
The authors declare no competing interests.
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Green, E.D., Gunter, C., Biesecker, L.G. et al. Strategic vision for improving human health at The Forefront of Genomics. Nature 586, 683–692 (2020). https://doi.org/10.1038/s41586-020-2817-4
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