Integrated Framework to Annotate Genetic Variants

The 'annovarR' package provides R functions as well as database resources which offer an integrated framework to annotate genetic variants from genome and transcriptome data. The wrapper functions of 'annovarR' unified the interface of many published annotation tools, such as 'VEP' (< http://asia.ensembl.org/info/docs/tools/vep/index.html>), 'ANNOVAR' (< http://annovar.openbioinformatics.org/>), 'vcfanno' (< https://github.com/brentp/vcfanno>) and 'AnnotationDbi' (< http://www.bioconductor.org/packages/release/bioc/html/AnnotationDbi.html>). It also simplified the use of some of the external annotation tools in R. Besides, massive published genetic variants annotation databases were integrated into 'annovarR'. For example, 'annovarR' provides a newly RNA-seq allele frequency database, BRVar, which built from total 1,285 cases public B-progenitor acute lymphoblastic leukemia (B-ALL) transcriptome data.


annovarR is an integrated open source tool to annotate genetic variants data based on ANNOVAR and other public annotation databases, such as varcards, REDIportal, .etc.

The main development motivation of annovarR is to increase the supported database and facilitate the variants annotation work. There are already too many tools and databases available and the usage is quite different. annovarR will integrate these annotation tools and get the merged annotation result in R.

annovarR will not only provide annotation functions (both internal and external) but also established an annotation database pool including published and community contributed.

In addition, to provide more transcription levels of variant database resources, we collected total 1,285 cases public B-progenitor acute lymphoblastic leukemia (B-ALL) transcriptome data from five different published datasets and built a novel large-scale transcript level sequencing variant database. The Genome Analysis Toolkit (GATK), VarScan2 and LoFreq be used to call variants from the RNA-seq data (Database called BRVar). This work can help us to screen candidate systematic sequencing bias and evaluate variant calling trait from B-ALL RNA-seq.

If you want to download the 1,285 RNA-seq variants frequency database, you need click here and send us a short application message (Whether it is for commercial use?). If the application is applied, we will reply you within 24 hours with a download required license code.

# Download BRVar database
# You must input the applied license code
library(annovarR)
download.database("db_annovar_brvar", "/path/annovar.dir",  license = "licence_code")

Requirements

annovarR annotation system:

ANNOVAR annotation system:

VEP annotation system

vcfanno annotationo system

Installation

Core softwares

# CRAN to install annovarR (The R package BioInstaller will be installed)
setRepositories(ind=1:2)
install.packages('annovarR')
 
# Github to install annovarR (The R package BioInstaller will be installed)
# install.packages("devtools")
devtools::install_github("JhuangLab/annovarR")
 
# Use BioInstaller to install ANNOVAR easily in R
library(BioInstaller)
install.bioinfo('annovar', '/path/annovar.dir')
 
# Use BioInstaller to install vcfanno easily in R
install.bioinfo('vcfanno', '/path/vcfanno.dir')

Annotation Database

# Use download.database to download databases supported by annovarR and ANNOVAR
# Some of examples as shown as below
library(annovarR)
download.database('db_annovar_refgene', database.dir = "/path/database.dir/humandb", buildver = "hg19")
download.database('db_ucsc_cytoband', database.dir = "/path/database.dir/humandb", buildver = "hg19")
download.database('db_annovar_avsnp147', database.dir = "/path/database.dir/humandb", buildver = "hg19")
# Or
download.database(c("db_annovar_refgene", "db_ucsc_cytoband"), 
  database.dir = "/path/database.dir/humandb", buildver = "hg19")
 
# All annovarR supported big annotation database required SQLite format
download.database('db_annovar_avsnp147_sqlite', database.dir = "/path/database.dir/humandb", buildver = "hg19")

Support Summary

  • ANNOVAR databases
  • 1285 cases B-ALL RNA-seq variants
  • Public RNA-editing databases
  • Other public database

Basic Usage

# View the vignettes in annovarR package
browseVignettes("annovarR")
 
# Get all annovarR supported annotation name
get.annotation.names()
 
# Get annotation name needed download.name and 
# you can use download.database to download database using the download.name.
download.name <- get.download.name('avsnp147')
 
# Show download.name avaliable all versions database
download.database(download.name = download.name, show.all.versions = TRUE)
# Download database in annotation database directory
# Buildver default is hg19
download.database(download.name = download.name, version = "avsnp147", buildver = "hg19", 
  database.dir = "/path/database.dir")
 
# Annotate variants from avsnp147 database use annovarR
library(data.table)
database.dir <- "/path/database.dir"
chr <- c("chr1", "chr2", "chr1")
start <- c("10020", "10020", "10020")
end <- c("10020", "10020", "10020")
ref <- c("A", "A", "A")
alt <- c("-", "-", "-")
database.dir <- tempdir()
dat <- data.table(chr = chr, start = start, end = end, ref = ref, alt = alt)
x <- annotation(dat = dat, anno.name = "avsnp147", database.dir = database.dir)
 
# Annotate using multiple database
x <- annotation.merge(dat = dat, anno.names = c("cosmic81", "avsnp147"), database.dir = database.dir)
 
# Database configuration file
database.cfg <- system.file('extdata', 'config/databases.toml', package = "annovarR")
 
# Get anno.name needed input cols
get.annotation.needcols('avsnp147')
 
# Annotate avinput format R data and file using ANNOVAR
annovar.dir <- "/opt/bin/annovar"
database.dir <- "/opt/bin/annovar/humandb"
chr = "chr1"
start = "123"
end = "123"
ref = "A"
alt = "C"
dat <- data.table(chr, start, end, ref, alt)
tmpfn <- tempfile()
write.table(dat, fn, row.names = FALSE, quote = FALSE, sep = "\t", col.names = FALSE)
x <- annotation(dat, "perl_annovar_refGene", annovar.dir = "/opt/bin/annovar", 
             database.dir = database.dir)
x <- annotation(input.file = tmpfn, "perl_annovar_refGene", annovar.dir = "/opt/bin/annovar", 
             database.dir = database.dir)
 
# Annotate avinput format R data using annovarR and ANNOVAR
# It will return a list contatin two data.table object that 
# one is annovarR annotation system and the another is ANNOVAR output 
x <-annotation.merge(dat = dat, anno.names = c('avsnp147', 'perl_annovar_refGene'), 
  annovar.dir = annovar.dir, database.dir = database.dir)
x <- annotation.merge(dat = dat, anno.names = c('avsnp147', '1000g2015aug_all', 
  'perl_annovar_refGene', 'perl_annovar_ensGene'), annovar.dir = annovar.dir, database.dir = database.dir)
# If use perl_annovar_merge as the anno.name, you can use annovar.anno.names to 
# run all original ANNOVAR supported annotation names, see http://annovar.openbioinformatics.org/en/latest/user-guide/download/
x <- annotation.merge(dat = dat, anno.names = c('avsnp147', '1000g2015aug_all', 
  'perl_annovar_merge'), annovar.anno.names = c('refGene', 'ensGene'), annovar.dir = annovar.dir, database.dir = database.dir)
 
# Annotate VCF file using ANNOVAR
x <- annotation(anno.name = "perl_annovar_ensGene", input.file = "/tmp/test.vcf",
             annovar.dir = annovar.dir, database.dir = "{{annovar.dir}}/humandb", 
             out = tempfile(), vcfinput = TRUE)
 
# Annotation VCF file use VEP
vep(debug = TRUE)
x <- annotation(anno.name = "vep_all", input.file = "/tmp/test.vcf",
             out = tempfile())
 
# Annotation VCF file use vcfanno
vcfanno(debug = TRUE)
x <- annotation(anno.name = "vcfanno_demo")
annotation(anno.name = "vcfanno_demo", input.file = system.file("extdata", "demo/vcfanno_demo/query.vcf.gz", 
                   package = "annovarR"), out = "test.vcf", vcfanno = "/path/vcfanno")
 
# Annotate gene using BioConductor database
# The example below will use the org.Hs.eg.db to get the alias of TP53 and NSD2
# It is more simple than the previous annotation API
gene <- c("TP53", "NSD2")
x <- annotation(dat = gene, anno.name = "bioc_gene2alias")
 
# Do same things use AnnotationDbi
library(org.Hs.eg.db)
library(AnnotationDbi)
select(keys = gene, keytype = "SYMBOL", columns = "ALIAS")
 

Docker

You can use the annovarR in Docker.

docker pull bioinstaller/annovarr:develop
docker run -it -v /tmp/db:/tmp/db -v /tmp/input:/tmp/input bioinstaller/annovarr:develop R

How to contribute?

Please fork the GitHub annovarR repository, modify it, and submit a pull request to us.

Maintainer

Jianfeng Li

License

R package:

MIT

Related Other Resources:

Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License

News

annovarR 1.0.0

Functions

  • Supported external tools (vep, vcfanno, ANNOVAR, AnnotationDBI)
  • Developed R data matching functions annotation.cols.match and annotation.region.match
  • Unified annotation API annotation and annotation.merge

Databases

  • Supported 80 types annotation database download (Exclude BioConductor Package)
  • Supported 181 annotation shortcut using R function and external tools
  • Introduced the 1285 cases B-cell acute lymphoblastic leukemia RNA-seq variants (brvar_v1_core and brvar_v1_extra)

Issues

  • supported 1.10.4.3 data.table in released and 64-bit development version of R

Reference manual

It appears you don't have a PDF plugin for this browser. You can click here to download the reference manual.

install.packages("annovarR")

1.0.0 by Jianfeng Li, a year ago


https://github.com/JhuangLab/annovarR


Report a bug at https://github.com/JhuangLab/annovarR/issues


Browse source code at https://github.com/cran/annovarR


Authors: Jianfeng Li [aut, cre]


Documentation:   PDF Manual  


MIT + file LICENSE license


Imports stringr, configr, BioInstaller, ngstk, DBI, data.table, RSQLite, futile.logger, stringi, RMySQL, vcfR, AnnotationDbi, glue, methods

Suggests testthat, knitr, rmarkdown, org.Hs.eg.db


See at CRAN