Ultrafast and scalable variant annotation and prioritization with big functional genomics data

Dandan Huang, Xianfu Yi, Yao Zhou, Hongcheng Yao, Hang Xu, Jianhua Wang, Shijie Zhang, Wenyan Nong, Panwen Wang, Lei Shi, Chenghao Xuan, Miaoxin Li, Junwen Wang, Weidong Li, Hoi Shan Kwan, Pak Chung Sham, Kai Wang, Mulin Jun Li

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1789-1801
Number of pages13
JournalGenome Research
Volume31
Issue number12
DOIs
StatePublished - Oct 15 2020

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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