VarNote is a tool to rapidly annotate genome-scale variants from large and complex functional annotation resources. VarNote is equipped by a novel index system and a parallel random-sweep searching algorithm. It shows substantial performance improvements to annotate human genetic variants at different scales. VarNote supports both region-based and allele-specific annotations for different file formats and equips many advanced functions for flexible annotations extraction. By integrating massive allele-specific annotations and our functional/pathogenic regulatory variant prediction models in VarNote web portal, biologists and clinicians can simply achieve fast and comprehensive functional/pathogenic regulatory variant/mutation prioritization using genome-scale inputs.

Genome-scale Variant Prioritization Applications

The advanced features of VarNote enable it can be extended to efficiently annotate and prioritize whole-genome non-coding variants in different genetic studies, such as GWAS downstream analysis and whole-genome sequencing of patients with inherited diseases. We leveraged VarNote programming APIs and large-scale variant annotations to provide three commonly-used applications, including

  1. VarNote-REG: prioritization of likely causal regulatory variants from GWAS results;
  2. VarNote-PAT: prioritization of rare pathogenic regulatory variants from WES/WGS of patients with inherited diseases;
  3. VarNote-CAN: prioritization of cancer driver regulatory mutations from tumor sequencing results.
VarNote-REG

By integrating 127 Roadmap tissue/cell type-specific epigenomic profiles and 5 tissue/cell type-specific prediction tools (including cepip, GenoSkylinePlus, FUN-LDA, FitCons2, GenoNet), VarNote-REG can efficiently prioritize causal regulatory variants in the LD of each GWAS signal and provide combined scores.

VarNote-PAT

By introducing VarNote filtrations on allele frequency, genetic inheritance model and genomic features, VarNote-PAT can significantly reduce the analytical time for WGS/WES data. Using combination scores, VarNote-PAT also showed improved performance in prioritizing true pathogenic regulatory variants of inherited diseases.

VarNote-CAN

By annotating somatic recurrence of cancer non-coding regulatory mutations and incorporating our regBase-CAN cancer driver regulatory mutation prediction model, VarNote-CAN can prioritize likely cancer driver regulatory mutation given personal cancer genome profile.

Please cite VarNote as follows:

Huang D, Yi X, Zhou Y, Yao H, Xu H, Wang J, Zhang S, Nong W, Wang P, Shi L, Xuan C, Li M, Wang J, Li W, Kwan HS, Sham PC, Wang K, Li MJ*. Ultrafast and scalable variant annotation and prioritization with big functional genomics data. Genome Res. 2020 Dec;30(12):1789-1801.