Ultrafast and scalable variant annotation and prioritization with big functional genomics data
- Dandan Huang1,2,3,
- Xianfu Yi4,
- Yao Zhou2,
- Hongcheng Yao5,
- Hang Xu1,5,
- Jianhua Wang2,
- Shijie Zhang2,
- Wenyan Nong6,
- Panwen Wang7,
- Lei Shi3,
- Chenghao Xuan3,
- Miaoxin Li8,
- Junwen Wang7,
- Weidong Li9,
- Hoi Shan Kwan6,
- Pak Chung Sham10,
- Kai Wang11 and
- Mulin Jun Li1,2,12
- 1The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin 300070, China;
- 2Department of Pharmacology, Tianjin Key Laboratory of Inflammation Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China;
- 3Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China;
- 4School of Biomedical Engineering, Tianjin Medical University, Tianjin 300070, China;
- 5School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR 999077, China;
- 6School of Life Sciences, The Chinese University of Hong Kong, Hong Kong SAR 999077, China;
- 7Department of Health Sciences Research and Center for Individualized Medicine, Mayo Clinic, Scottsdale, Arizona 85259, USA;
- 8Center for Genome Research, Center for Precision Medicine, Zhongshan School of Medicine, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China;
- 9Department of Genetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China;
- 10Centre of Genomics Sciences, Departments of Psychiatry, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR 999077, China;
- 11Raymond G. Perelman Center for Cellular and Molecular Therapeutics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA;
- 12Department of Epidemiology and Biostatistics, Tianjin Key Laboratory of Molecular Cancer Epidemiology, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin 300070, China
Abstract
The advances of large-scale genomics studies have enabled compilation of cell type–specific, genome-wide DNA functional elements at high resolution. With the growing volume of functional annotation data and sequencing variants, existing variant annotation algorithms lack the efficiency and scalability to process big genomic data, particularly when annotating whole-genome sequencing variants against a huge database with billions of genomic features. Here, we develop VarNote to rapidly annotate genome-scale variants in large and complex functional annotation resources. Equipped with a novel index system and a parallel random-sweep searching algorithm, VarNote shows substantial performance improvements (two to three orders of magnitude) over existing algorithms at different scales. It supports both region-based and allele-specific annotations and introduces advanced functions for the flexible extraction of annotations. By integrating massive base-wise and context-dependent annotations in the VarNote framework, we introduce three efficient and accurate pipelines to prioritize the causal regulatory variants for common diseases, Mendelian disorders, and cancers.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.267997.120.
- Received June 28, 2020.
- Accepted September 22, 2020.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
