FAVOR: functional annotation of variants online resource and annotator for variation across the human genome

Author:

Zhou Hufeng1ORCID,Arapoglou Theodore1,Li Xihao1ORCID,Li Zilin12ORCID,Zheng Xiuwen3,Moore Jill4,Asok Abhijith5,Kumar Sushant67,Blue Elizabeth E89,Buyske Steven10,Cox Nancy11,Felsenfeld Adam12,Gerstein Mark1314,Kenny Eimear151617,Li Bingshan18ORCID,Matise Tara19,Philippakis Anthony20,Rehm Heidi L2122,Sofia Heidi J12,Snyder Grace12,Weng Zhiping4,Neale Benjamin2123,Sunyaev Shamil R2124,Lin Xihong12125ORCID,

Affiliation:

1. Department of Biostatistics, Harvard T.H. Chan School of Public Health , Boston , MA , USA

2. Department of Biostatistics and Health Data Science, Indiana University School of Medicine , Indianapolis , IN, USA

3. Department of Biostatistics, University of Washington , Seattle , WA  98195, USA

4. Program in Bioinformatics and Integrative Biology, University of Massachusetts Chan Medical School , Worcester , MA , USA

5. Microsoft Inc. Redmond , WA, USA

6. Department of Medical Biophysics, University of Toronto , Toronto , ON, Canada

7. Princess Margaret Cancer Centre , Toronto , ON, Canada

8. Division of Medical Genetics, University of Washington , Seattle , WA , USA

9. Brotman Baty Institute for Precision Medicine , Seattle , WA , USA

10. Department of Statistics, Rutgers, The State University of New Jersey , Piscataway, NJ, USA

11. Department of Medicine, Vanderbilt University Medical Center , Nashville , TN, USA

12. National Human Genome Research Institute , Bethesda , DC, USA

13. Program in Computational Biology and Bioinformatics, Yale University , New Haven , CT, USA

14. Department of Molecular Biophysics and Biochemistry, Yale University , New Haven , CT, USA

15. Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai , New York , NY , USA

16. Department of Medicine, Icahn School of Medicine at Mount Sinai , New York , NY , USA

17. Institute for Genomic Health, Icahn School of Medicine at Mount Sinai , New York , NY , USA

18. Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center , Nashville , TN, USA

19. Department of Genetics, Rutgers, The State University of New Jersey , Piscataway, NJ, USA

20. Data Science Platform, Broad Institute of Harvard and MIT , Cambridge , MA , USA

21. Program in Medical and Population Genetics, Broad Institute of Harvard and MIT , Cambridge , MA , USA

22. Center for Genomic Medicine, Massachusetts General Hospital , Boston , MA , USA

23. Analytic and Translational Genetics Unit, Massachusetts General Hospital , Boston , MA , USA

24. Department of Biomedical Informatics, Harvard Medical School , Boston , MA , USA

25. Department of Statistics, Harvard University , Cambridge , MA , USA

Abstract

Abstract Large biobank-scale whole genome sequencing (WGS) studies are rapidly identifying a multitude of coding and non-coding variants. They provide an unprecedented resource for illuminating the genetic basis of human diseases. Variant functional annotations play a critical role in WGS analysis, result interpretation, and prioritization of disease- or trait-associated causal variants. Existing functional annotation databases have limited scope to perform online queries and functionally annotate the genotype data of large biobank-scale WGS studies. We develop the Functional Annotation of Variants Online Resources (FAVOR) to meet these pressing needs. FAVOR provides a comprehensive multi-faceted variant functional annotation online portal that summarizes and visualizes findings of all possible nine billion single nucleotide variants (SNVs) across the genome. It allows for rapid variant-, gene- and region-level queries of variant functional annotations. FAVOR integrates variant functional information from multiple sources to describe the functional characteristics of variants and facilitates prioritizing plausible causal variants influencing human phenotypes. Furthermore, we provide a scalable annotation tool, FAVORannotator, to functionally annotate large-scale WGS studies and efficiently store the genotype and their variant functional annotation data in a single file using the annotated Genomic Data Structure (aGDS) format, making downstream analysis more convenient. FAVOR and FAVORannotator are available at https://favor.genohub.org.

Funder

National Human Genome Research Institute

National Cancer Institute

National Heart, Lung, and Blood Institute

Publisher

Oxford University Press (OUP)

Subject

Genetics

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