vcfanno

README

vcfanno

vcfanno annotates a VCF with any number of sorted input BED, BAM, and VCF files. It does this by finding overlaps as it streams over the data and applying user-defined operations on the overlapping fields.

For VCF, values are pulled by name from the INFO field. For BED, values are pulled from (1-based) column number. For BAM, only depth (count) is currently supported.

vcfanno is written in go It can annotate ~ 5,000 variants per second with 5 annotations from 3 files on a modest laptop.

We are actively developing vcfanno and appreciate feedback and bug reports.

Usage

After downloading the binary for your system (see section below) usage looks like:

  ./vcfanno example/conf.toml example/query.vcf

Where config.toml looks like:

[[annotation]]
file="ExAC.vcf"
fields = ["AC_AFR", "AC_AMR", "AC_EAS"]
ops=["first", "first", "min"]

[[annotation]]
file="fitcons.bed"
columns = [4]
names=["fitcons_mean"]
ops=["mean"]

[[annotation]]
file="example/ex.bam"
names=["ex_bam_depth"]
#count is currently the only valid option for a bam

So from ExAC.vcf we will pull the fields from the info field and apply the corresponding operation from the ops array. Users can add as many [[annotation]] blocks to the conf file as desired. Files can be local as above, or available via http/https.

Also see the additional usage section at the bottom for additional details.

Example

the example directory contains the data and conf for a full example. To run, either download the appropriate binary for your system build with:

go get
go build -o vcfanno

from this directory. Then, you can annotate with:

GOMAXPROCS=4 ./vcfanno example/conf.toml example/query.vcf > annotated.vcf

An example INFO field row before annotation (pos 98683):

AB=0.282443;ABP=56.8661;AC=11;AF=0.34375;AN=32;AO=45;CIGAR=1X;TYPE=snp

and after:

AB=0.2824;ABP=56.8661;AC=11;AF=0.3438;AN=32;AO=45;CIGAR=1X;TYPE=snp;AC_AFR=0;AC_AMR=0;AC_EAS=0;fitcons_mean=0.061

Operations

In most cases, we will have a single annotation entry for each entry (variant) in the query VCF. However, it is possible that there will be multiple annotations from a single annotation file--in this case, the op determines how the many values are reduced. Valid operations are:

• mean
• max
• min
• concat // comma delimited list of output
• count // count the number of overlaps
• uniq
• first
• flag // presense/absence via vcf flag

Please open an issue if your desired operation is not supported.

Binaries

binary executables are available here for linux, mac (darwin), and windows for 32 and 64 bit platforms.

Preprocessing

Annotations will be the most accurate if your query and annotation variants are split (no multiple ALTs) and normalize (left-aligned and trimmed). At some point, this will be done internally, but for now, you can get a split and normalized VCF using vt with:

vt decompose -s $VCF | vt normalize -r $REF - > $NORM_VCF

Development

This, and the associated go libraries (vcfgo, irelate, xopen) are under active development. The following are on our radar:

• decompose, normalize, and get allelic primitives for variants on the fly (we have code to do this, it just needs to be integrated)
• improve test coverage for vcfanno
• embed v8 to allow custom ops.
• support for annotating BED files (coming in v0.0.3)

Additional Usage

-ends

For annotating large variants, such as CNVs or structural variants (SVs), it can be useful to annotate the ends of the variant in addition to the region itself. To do this, specify the -ends flag to vcfanno. e.g.:

vcfanno -ends example/conf.toml example/query.vcf

In this case, the names field in the conf file contains, "fitcons_mean". The output will contain fitcons\_mean as before along with left\_fitcons\_mean and right\_fitcons\_mean for any variants that are longer than 1 base. The left end will be for the single-base at the lowest base of the variant and the right end will be for the single base at the higher numbered base of the variant.

-permissive-overlap

By default, when annotating with a variant, in addition to the overlap requirement, the variants must share the same position, the same reference allele and at least one alternate allele (this is only used for variants, not for BED/BAM annotations). If this flag is specified, only overlap testing is used and shared REF/ALT are not required.

vcfanno -permissive-overlap example/conf.toml example/query.vcf