haploblock-shuffler 0.0.6

Create all possible combinations of phased and unphased blocks in a vcf

Haploblock-shuffler

Create all possible combinations of phased and unphased blocks in a vcf

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Background

This tool takes a phase, unphased or partially phased VCF file, and generates all possible combinations of phase blocks that are consistent with the phasing that is present in the VCF file.

Details

First, this tool reads all variants from a VCF file, and groups variants together if they are compatible.

1. If a variant is phased (using the PS tag), it is only compatible with other phased variants that have the same phase ID.
2. Homozygous variants are always compatible with other variants, since they are part of every phase group
3. Heterozygous variants are only compatible when they are phased, and the phase ID matches.

To produce all possible combinations of grouped variants, haplotype-suffler uses a counter to produce a binary pattern that determines which calls should be modified. To modify a variant, we simply invert the order of the GT field, so that 0/1 becomes 1/0, or vice versa.

Since there are two alleles for every variant, we only have to produce half of the possible VCF file, since the other half are mirror images (e.g. 0101 and 1010).

Usage

haploblock-shuffler test.vcf output

To generate consensus fasta files from the output vcf files, bgzip and index the output vcf files

cd output
for i in out_*.vcf; do
    bgzip $i
    tabix ${i}.gz
done

Then, generate the consensus using

samtools faidx $REFERENCE $REGION | bcftools consensus -H 1 out_0.vcf.gz > out_0_1.fa
samtools faidx $REFERENCE $REGION | bcftools consensus -H 2 out_0.vcf.gz > out_0_2.fa

Limitations

This tool will generate 2^(n-1) VCF files in the specified output folder, where n is the number of phase blocks in the input VCF (see above). By default, this is limited to 11 blocks, which means that at most 1024 files will be created. This limit can be increased by using --max-blocks, but use with caution.