Variant Call Format

The Variant Call Format (VCF) specifies the format of a text file used in bioinformatics for storing gene sequence variations. The format has been developed with the advent of large-scale genotyping and DNA sequencing projects, such as the 1000 Genomes Project. Existing formats for genetic data such as General feature format (GFF) stored all of the genetic data, much of which is redundant because it will be shared across the genomes. By using the variant call format only the variations need to be stored along with a reference genome.

Variant Call Format
Developed byVCFtools
Type of formatBioinformatics
Extended fromTab-separated values
Open format?yes
Websitegithub.com/samtools/hts-specs

The standard is currently in version 4.3,[1][2] although the 1000 Genomes Project has developed its own specification for structural variations such as duplications, which are not easily accommodated into the existing schema.[3] There is also a Genomic VCF (gVCF) extended format, which includes additional information about "blocks" that match the reference and their qualities.[4] A set of tools is also available for editing and manipulating the files.[5] [6]

Example

##fileformat=VCFv4.3
##fileDate=20090805
##source=myImputationProgramV3.1
##reference=file:///seq/references/1000GenomesPilot-NCBI36.fasta
##contig=<ID=20,length=62435964,assembly=B36,md5=f126cdf8a6e0c7f379d618ff66beb2da,species="Homo sapiens",taxonomy=x>
##phasing=partial
##INFO=<ID=NS,Number=1,Type=Integer,Description="Number of Samples With Data">
##INFO=<ID=DP,Number=1,Type=Integer,Description="Total Depth">
##INFO=<ID=AF,Number=A,Type=Float,Description="Allele Frequency">
##INFO=<ID=AA,Number=1,Type=String,Description="Ancestral Allele">
##INFO=<ID=DB,Number=0,Type=Flag,Description="dbSNP membership, build 129">
##INFO=<ID=H2,Number=0,Type=Flag,Description="HapMap2 membership">
##FILTER=<ID=q10,Description="Quality below 10">
##FILTER=<ID=s50,Description="Less than 50% of samples have data">
##FORMAT=<ID=GT,Number=1,Type=String,Description="Genotype">
##FORMAT=<ID=GQ,Number=1,Type=Integer,Description="Genotype Quality">
##FORMAT=<ID=DP,Number=1,Type=Integer,Description="Read Depth">
##FORMAT=<ID=HQ,Number=2,Type=Integer,Description="Haplotype Quality">
#CHROM POS      ID         REF   ALT    QUAL  FILTER   INFO                             FORMAT       NA00001         NA00002          NA00003
20     14370    rs6054257  G     A      29    PASS    NS=3;DP=14;AF=0.5;DB;H2           GT:GQ:DP:HQ  0|0:48:1:51,51  1|0:48:8:51,51   1/1:43:5:.,.
20     17330    .          T     A      3     q10     NS=3;DP=11;AF=0.017               GT:GQ:DP:HQ  0|0:49:3:58,50  0|1:3:5:65,3     0/0:41:3
20     1110696  rs6040355  A     G,T    67    PASS    NS=2;DP=10;AF=0.333,0.667;AA=T;DB GT:GQ:DP:HQ  1|2:21:6:23,27  2|1:2:0:18,2     2/2:35:4
20     1230237  .          T     .      47    PASS    NS=3;DP=13;AA=T                   GT:GQ:DP:HQ  0|0:54:7:56,60  0|0:48:4:51,51   0/0:61:2
20     1234567  microsat1  GTC   G,GTCT 50    PASS    NS=3;DP=9;AA=G                    GT:GQ:DP     0/1:35:4        0/2:17:2         1/1:40:3

The VCF header

The header begins the file and provides metadata describing the body of the file. Header lines are denoted as starting with #. Special keywords in the header are denoted with ##. Recommended keywords include fileformat, fileDate and reference.

The header contains keywords that optionally semantically and syntactically describe the fields used in the body of the file, notably INFO, FILTER, and FORMAT (see below).

The columns of a VCF

The body of VCF follows the header, and is tab separated into 8 mandatory columns and an unlimited number of optional columns that may be used to record other information about the sample(s). When additional columns are used, the first optional column is used to describe the format of the data in the columns that follow.

NameBrief description (see the specification for details).
1CHROMThe name of the sequence (typically a chromosome) on which the variation is being called. This sequence is usually known as 'the reference sequence', i.e. the sequence against which the given sample varies.
2POSThe 1-based position of the variation on the given sequence.
3IDThe identifier of the variation, e.g. a dbSNP rs identifier, or if unknown a ".". Multiple identifiers should be separated by semi-colons without white-space.
4REFThe reference base (or bases in the case of an indel) at the given position on the given reference sequence.
5ALTThe list of alternative alleles at this position.
6QUALA quality score associated with the inference of the given alleles.
7FILTERA flag indicating which of a given set of filters the variation has passed.
8INFO    An extensible list of key-value pairs (fields) describing the variation. See below for some common fields. Multiple fields are separated by semicolons with optional values in the format: <key>=<data>[,data].
9FORMATAn (optional) extensible list of fields for describing the samples. See below for some common fields.
+SAMPLEsFor each (optional) sample described in the file, values are given for the fields listed in FORMAT

Common INFO fields

Arbitrary keys are permitted, although the following sub-fields are reserved (albeit optional)[1]:

NameBrief description
AAancestral allele
ACallele count in genotypes, for each ALT allele, in the same order as listed
AFallele frequency for each ALT allele in the same order as listed (use this when estimated from primary data, not called genotypes)
ANtotal number of alleles in called genotypes
BQRMS base quality at this position
CIGARcigar string describing how to align an alternate allele to the reference allele
DBdbSNP membership
DPcombined depth across samples, e.g. DP=154
ENDend position of the variant described in this record (for use with symbolic alleles)
H2membership in hapmap2
H3membership in hapmap3
MQRMS mapping quality, e.g. MQ=52
MQ0Number of MAPQ == 0 reads covering this record
NSNumber of samples with data
SBstrand bias at this position
SOMATICindicates that the record is a somatic mutation, for cancer genomics
VALIDATEDvalidated by follow-up experiment
1000Gmembership in 1000 Genomes

Common FORMAT fields

NameBrief description
ADRead depth for each allele
ADFRead depth for each allele on the forward strand
ADRRead depth for each allele on the reverse strand
DPRead depth
ECExpected alternate allele counts
FTFilter indicating if this genotype was “called”
GLGenotype likelihoods
GPConditional genotype quality
GQConditional genotype quality
GTGenotype
HQHaplotype quality
MQRMS mapping quality
PLPhred-scaled genotype likelihoods rounded to the closest integer
PQPhasing quality
PSPhase set
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See also

  • The FASTA format, used to represent genome sequences.
  • The FASTQ format, used to represent DNA sequencer reads along with quality scores.
  • The SAM format, used to represent genome sequencer reads that have been aligned to genome sequences.
  • The GVF format (Genome Variation Format), an extension based on the GFF3 format.

The VCF specification is no longer maintained by the 1000 Genomes Project. The group leading the management and expansion of the format is the Global Alliance for Genomics and Health (GA4GH) Large Scale Genomics Work Stream file format team[7], http://ga4gh.org/#/fileformats-team

  • An explanation of the format in picture form
  • Ossola, Alexandra (20 March 2015). "The Race to Build a Search Engine for Your DNA". IEEE Spectrum. Retrieved March 2015. Check date values in: |access-date= (help)

References

  1. "VCF Specification" (PDF). Retrieved 20 Oct 2016.
  2. "Specifications of SAM/BAM and related high-throughput sequencing file formats". Retrieved 24 June 2014.
  3. "Encoding Structural Variants in VCF (Variant Call Format) version 4.0 | 1000 Genomes". Retrieved 20 October 2016.
  4. "GVCF - Genomic Variant Call Format". GATK. Broad Institute.
  5. "VCFtools from Github.io". Retrieved 20 October 2016.
  6. "BCFtools".
  7. "Bio-IT World". www.bio-itworld.com. Retrieved 2018-10-26.
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