NAME

vcflib index

DESCRIPTION

vcflib contains tools and libraries for dealing with the Variant Call Format (VCF) which is a flat-file, tab-delimited textual format intended to describe reference-indexed variations between individuals.

VCF provides a common interchange format for the description of variation in individuals and populations of samples, and has become the defacto standard reporting format for a wide array of genomic variant detectors.

vcflib provides methods to manipulate and interpret sequence variation as it can be described by VCF. It is both:

•: an API for parsing and operating on records of genomic variation as it can be described by the VCF format,
•: and a collection of command-line utilities for executing complex manipulations on VCF files.

The API itself provides a quick and extremely permissive method to read and write VCF files. Extensions and applications of the library provided in the included utilities (*.cpp) comprise the vast bulk of the library’s utility for most users.

filter

filter command	description
vcffilter	VCF filter the specified vcf file using the set of filters
vcfuniq	List unique genotypes. Similar to GNU uniq, but aimed at VCF records. vcfuniq removes records which have the same position, ref, and alt as the previous record on a sorted VCF file. Note that it does not adjust/combine genotypes in the output, but simply takes the first record. See also vcfcreatemulti for combining records.
vcfuniqalleles	List unique alleles For each record, remove any duplicate alternate alleles that may have resulted from merging separate VCF files.

metrics

metrics command	description
vcfcheck	Validate integrity and identity of the VCF by verifying that the VCF record’s REF matches a given reference file.
vcfdistance	Adds a tag to each variant record which indicates the distance to the nearest variant. (defaults to BasesToClosestVariant if no custom tag name is given.
vcfentropy	Annotate VCF records with the Shannon entropy of flanking sequence. Anotates the output VCF file with, for each record, EntropyLeft, EntropyRight, EntropyCenter, which are the entropies of the sequence of the given window size to the left, right, and center of the record. Also adds EntropyRef and EntropyAlt for each alt.
vcfhetcount	Calculate the heterozygosity rate: count the number of alternate alleles in heterozygous genotypes in all records in the vcf file
vcfhethomratio	Generates the het/hom ratio for each individual in the file

phenotype

phenotype command	description
permuteGPAT++	permuteGPAT++ is a method for adding empirical p-values to a GPAT++ score.

genotype

genotype command	description
abba-baba	abba-baba calculates the tree pattern for four indviduals. This tool assumes reference is ancestral and ignores non abba-baba sites. The output is a boolian value: 1 = true , 0 = false for abba and baba. the tree argument should be specified from the most basal taxa to the most derived.
hapLrt	HapLRT is a likelihood ratio test for haplotype lengths. The lengths are modeled with an exponential distribution. The sign denotes if the target has longer haplotypes (1) or the background (-1).
normalize-iHS	normalizes iHS or XP-EHH scores.

transformation

transformation command	description
dumpContigsFromHeader	Dump contigs from header
smoother	smoothes is a method for window smoothing many of the GPAT++ formats.
vcf2dag	Modify VCF to be able to build a directed acyclic graph (DAG)
vcf2fasta	Generates sample_seq:N.fa for each sample, reference sequence, and chromosomal copy N in [0,1... ploidy]. Each sequence in the fasta file is named using the same pattern used for the file name, allowing them to be combined.
vcf2tsv	Converts VCF to per-allelle or per-genotype tab-delimited format, using null string to replace empty values in the table. Specifying -g will output one line per sample with genotype information. When there is more than one alt allele there will be multiple rows, one for each allele and, the info will match the `A' index
vcfaddinfo	Adds info fields from the second file which are not present in the first vcf file.
vcfafpath	Display genotype paths
vcfallelicprimitives	WARNING: this tool is considered legacy and is only retained for older workflows. It will emit a warning! Even though it can use the WFA you should use vcfwave instead.
vcfannotate	Intersect the records in the VCF file with targets provided in a BED file. Intersections are done on the reference sequences in the VCF file. If no VCF filename is specified on the command line (last argument) the VCF read from stdin.
vcfannotategenotypes	Examine genotype correspondence. Annotate genotypes in the first file with genotypes in the second adding the genotype as another flag to each sample filed in the first file. annotation-tag is the name of the sample flag which is added to store the annotation. also adds a `has_variant' flag for sites where the second file has a variant.
vcfbreakmulti	If multiple alleles are specified in a single record, break the record into multiple lines, preserving allele-specific INFO fields.
vcfcat	Concatenates VCF files
vcfclassify	Creates a new VCF where each variant is tagged by allele class: snp, ts/tv, indel, mnp
vcfcleancomplex	Removes reference-matching sequence from complex alleles and adjusts records to reflect positional change.
vcfcombine	Combine VCF files positionally, combining samples when sites and alleles are identical. Any number of VCF files may be combined. The INFO field and other columns are taken from one of the files which are combined when records in multiple files match. Alleles must have identical ordering to be combined into one record. If they do not, multiple records will be emitted.
vcfcommonsamples	Generates each record in the first file, removing samples not present in the second
vcfcreatemulti	Go through sorted VCF and when overlapping alleles are represented across multiple records, merge them into a single multi-ALT record. See the documentation for more information.
vcfecho	Echo VCF to stdout (simple demo)
vcfevenregions	Generates a list of regions, e.g. chr20:10..30 using the variant density information provided in the VCF file to ensure that the regions have even numbers of variants. This can be use to reduce the variance in runtime when dividing variant detection or genotyping by genomic coordinates.
vcffixup	Generates a VCF stream where AC and NS have been generated for each record using sample genotypes
vcfflatten	Removes multi-allelic sites by picking the most common alternate. Requires allele frequency specification `AF' and use of `G' and `A' to specify the fields which vary according to the Allele or Genotype. VCF file may be specified on the command line or piped as stdin.
vcfgeno2alleles	modifies the genotypes field to provide the literal alleles rather than indexes
vcfgeno2haplo	Convert genotype-based phased alleles within –window-size into haplotype alleles. Will break haplotype construction when encountering non-phased genotypes on input.
vcfgenosamplenames	Get samplenames
vcfglbound	Adjust GLs so that the maximum GL is 0 by dividing all GLs for each sample by the max.
vcfglxgt	Set genotypes using the maximum genotype likelihood for each sample.
vcfindex	Adds an index number to the INFO field (id=position)
vcfinfo2qual	Sets QUAL from info field tag keyed by [key]. The VCF file may be omitted and read from stdin. The average of the field is used if it contains multiple values.
vcfinfosummarize	Take annotations given in the per-sample fields and add the mean, median, min, or max to the site-level INFO.
vcfintersect	VCF 1.0.12 set analysis
vcfkeepgeno	Reduce file size by removing FORMAT fields not listed on the command line from sample specifications in the output
vcfkeepinfo	To decrease file size remove INFO fields not listed on the command line
vcfkeepsamples	outputs each record in the vcf file, removing samples not listed on the command line
vcfld	Compute LD
vcfleftalign	Left-align indels and complex variants in the input using a pairwise ref/alt alignment followed by a heuristic, iterative left realignment process that shifts indel representations to their absolute leftmost (5’) extent.
vcflength	Add length info field
vcfnullgenofields	Makes the FORMAT for each variant line the same (uses all the FORMAT fields described in the header). Fills out per-sample fields to match FORMAT. Expands GT values of `.' with number of alleles based on ploidy (eg: `./.' for dipolid).
vcfnumalt	outputs a VCF stream where NUMALT has been generated for each record using sample genotypes
vcfoverlay	Overlay records in the input vcf files with order as precedence.
vcfprimers	For each VCF record, extract the flanking sequences, and write them to stdout as FASTA records suitable for alignment.
vcfqual2info	Puts QUAL into an info field tag keyed by [key].
vcfremap	For each alternate allele, attempt to realign against the reference with lowered gap open penalty. If realignment is possible, adjust the cigar and reference/alternate alleles. Observe how different alignment parameters, including context and entropy-dependent ones, influence variant classification and interpretation.
vcfremoveaberrantgenotypes	strips samples which are homozygous but have observations implying heterozygosity. Remove samples for which the reported genotype (GT) and observation counts disagree (AO, RO).
vcfremovesamples	outputs each record in the vcf file, removing samples listed on the command line
vcfsample2info	Take annotations given in the per-sample fields and add the mean, median, min, or max to the site-level INFO.
vcfsamplediff	Establish putative somatic variants using reported differences between germline and somatic samples. Tags each record where the listed sample genotypes differ with . The first sample is assumed to be germline, the second somatic. Each record is tagged with ={germline,somatic,loh} to specify the type of variant given the genotype difference between the two samples.
vcfsamplenames	List sample names
vcfstreamsort	Sorts the input (either stdin or file) using a streaming sort algorithm. Guarantees that the positional order is correct provided out-of-order variants are no more than 100 positions in the VCF file apart.
vcfwave	Realign reference and alternate alleles with WFA, parsing out the `primitive' alleles into multiple VCF records. New records have IDs that reference the source record ID. Genotypes/samples are handled correctly. Deletions generate haploid/missing genotypes at overlapping sites.

statistics

statistics command	description
bFst	bFst is a Bayesian approach to Fst. Importantly bFst accounts for genotype uncertainty in the model using genotype likelihoods. For a more detailed description see: `A Bayesian approach to inferring population structure from dominant markers’ by Holsinger et al. Molecular Ecology Vol 11, issue 7 2002. The likelihood function has been modified to use genotype likelihoods provided by variant callers. There are five free parameters estimated in the model: each subpopulation’s allele frequency and Fis (fixation index, within each subpopulation), a free parameter for the total population’s allele frequency, and Fst.
genotypeSummary	Generates a table of genotype counts. Summarizes genotype counts for bi-allelic SNVs and indel
iHS	iHS calculates the integrated haplotype score which measures the relative decay of extended haplotype homozygosity (EHH) for the reference and alternative alleles at a site (see: voight et al. 2006, Spiech & Hernandez 2014).
meltEHH
pFst	pFst is a probabilistic approach for detecting differences in allele frequencies between two populations.
pVst	pVst calculates vst, a measure of CNV stratification.
permuteSmooth	permuteSmooth is a method for adding empirical p-values smoothed wcFst scores.
plotHaps	plotHaps provides the formatted output that can be used with `bin/plotHaplotypes.R'.
popStats	General population genetic statistics for each SNP
segmentFst	segmentFst creates genomic segments (bed file) for regions with high wcFst
segmentIhs	Creates genomic segments (bed file) for regions with high wcFst
sequenceDiversity	The sequenceDiversity program calculates two popular metrics of haplotype diversity: pi and extended haplotype homozygoisty (eHH). Pi is calculated using the Nei and Li 1979 formulation. eHH a convenient way to think about haplotype diversity. When eHH = 0 all haplotypes in the window are unique and when eHH = 1 all haplotypes in the window are identical.
vcfaltcount	count the number of alternate alleles in all records in the vcf file
vcfcountalleles	Count alleles
vcfgenosummarize	Adds summary statistics to each record summarizing qualities reported in called genotypes. Uses: RO (reference observation count), QR (quality sum reference observations) AO (alternate observation count), QA (quality sum alternate observations)
vcfgenotypecompare	adds statistics to the INFO field of the vcf file describing the amount of discrepancy between the genotypes (GT) in the vcf file and the genotypes reported in the . use this after vcfannotategenotypes to get correspondence statistics for two vcfs.
vcfgenotypes	Report the genotypes for each sample, for each variant in the VCF. Convert the numerical represenation of genotypes provided by the GT field to a human-readable genotype format.
vcfparsealts	Alternate allele parsing method. This method uses pairwise alignment of REF and ALTs to determine component allelic primitives for each alternate allele.
vcfrandom	Generate a random VCF file
vcfrandomsample	Randomly sample sites from an input VCF file, which may be provided as stdin. Scale the sampling probability by the field specified in KEY. This may be used to provide uniform sampling across allele frequencies, for instance.
vcfroc	Generates a pseudo-ROC curve using sensitivity and specificity estimated against a putative truth set. Thresholding is provided by successive QUAL cutoffs.
vcfsitesummarize	Summarize by site
vcfstats	Prints statistics about variants in the input VCF file.
wcFst	wcFst is Weir & Cockerham’s Fst for two populations. Negative values are VALID, they are sites which can be treated as zero Fst. For more information see Evolution, Vol. 38 N. 6 Nov 1984. Specifically wcFst uses equations 1,2,3,4.

SOURCE CODE

See the source code repository at https://github.com/vcflib/vcflib

CREDIT

Citations are the bread and butter of Science. If you are using this software in your research and want to support our future work, please cite the following publication:

Please cite:

A spectrum of free software tools for processing the VCF variant call format: vcflib, bio-vcf, cyvcf2, hts-nim and slivar (https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1009123). Garrison E, Kronenberg ZN, Dawson ET, Pedersen BS, Prins P (2022), PLoS Comput Biol 18(5): e1009123. https://doi.org/10.1371/journal.pcbi.1009123

LICENSE

AUTHORS

Erik Garrison and vcflib contributors.