vg deconstruct (from vg) uses VCF info fields to describe how sites are nested in the original pangenome graph:
##INFO=<ID=LV,Number=1,Type=Integer,Description=\"Level in the snarl tree (0=top level)
##INFO=<ID=AT,Number=R,Type=String,Description=\"Allele Traversal as path in graph
##INFO=<ID=PS,Number=1,Type=String,Description=\"ID of variant corresponding to parent snarl
Given genotypes for a subset of sites from such a VCF, this tool uses these INFO fields to propagate the genotypes down to child sites of the genotyped sites. For example, consider these two sites from the deconstructed VCF, where the second is nested inside the first.
GRCh38.chr20 139949 >73154428>73154433 AAAGTC A,AAAGAC 60 . AC=3,1;AF=0.0337079,0.011236;AN=89;AT=>73154428>73154429>73154430>73154432>73154433,>73154428>73154433,>73154428>73154429<73154431>73154432>73154433;LV=0;
GRCh38.chr20 139953 >73154429>73154432 T A 60 . AC=1;AF=0.0116279;AN=86;AT=>73154429>73154430>73154432,>73154429<73154431>73154432;LV=1;PS=>73154428>73154433
The allele traversals are:
Parent
allele 0: >73154428>73154429>73154430>73154432>73154433
allele 1: >73154428>73154433
allele 2: >73154428>73154429<73154431>73154432>73154433
Child
allele 0: >73154429>73154430>73154432 (substring of parent allele 0)
allele 1: >73154429<73154431>73154432 (substring of parent allele 2)
This gives us the following mapping of all possible parent genotypes to child genotypes:
0/0 -> 0/0
0/1 -> 0/.
0/2 -> 0/1
1/1 -> ./.
1/2 -> ./1
2/2 -> 1/1
The intended use case is as follows
- extract all top-level sites from a deconstructed VCF (ex zcat
deconstruct.vcf.gz | grep -v PS | bgzip) - genotype the top-level sites with Pangenie
- infer genotypes of all nested sites from the top-level sites
Given a nested site, each of its alleles must be checked against each of its parent's alleles to determine the exact nesting relationship. Each check is substring match query of the child alleles AT string vs the parent's. For large bubbles, this is rather slow despite being multithreaded.
The output VCF will be annotated with this field (note that top-level bubbles are whatever's genotyped in the input and need not be LV=0)
Only LV=0 variants Will be used as input for PanGenie (PanGenie keeps IDs in INFO field, see below)
chr1 811390 . AATACAATGTTCTCCAGAAATAGTGTCGCAGAAATAAAGACAGAATATGGAAGGAGACAGGATTGCTGACTAATCTCATATGTACAGGGAGAACGACACTCCATGCAGCTTAGCTCCAACATGTGAGCGTGGGACAGAAAAGCAAGGTGAACCTAAAGACATCCCATGGACACACTGAGCTGGAACCAACTCTGCCCATAGGTGGTGGGGCCAGGTTCAGATGCTTGCAGTAACCGCATCCTCCTGTGAATCTGGGTCTACATGGCTGTGGCTCCCTGGGGGCTACCCACACTGTGGATTCCACAGGTGGAGGTGACCTTCTTGGGCACTGCTGGGACACTTCCTGGGCCTGCCTGGGCAGTGGTAGGGCTCAGAGAACTTCAGCGTTAGGGCCTTGGGGAGTCTATGTCAGACTTGAGGACAATACAATGTTCTCCAGAAATAGTGTCGCAGAAATAAAGACAGAATATGGAAGGAGACAGGATTGCTGACTAATCTCATATGTACAGGGAGAACGACACTCCATGCAGCTTAGCTCCAACATGTGAGTGTGGGACAGAAAAGCAAGGTGAACCTAAAGACATCCCATGGACACACTGAGCTGGAACCAACTCTGCCCATAGGTGGTGGGGCCAGGTTCAGATGCTTGCAGTAACCGCATCCTCCTGTGAATCTGGGTCTACATGGCTGTGGCTCCCTGGGGGCTACCCACACTGTGGATTCCACAGGTGGAGGTGACCTTCTTGGGCACTGCTGGGACACTTCTTGGGCCTGCCTGGGCAGTGGTAGGGCTCAGAGAACTTCAGCGTTAGGGCCTTGGGGAGTCTATGTCAGACTTGAGGAC,A,AATACAATGTTCTCCAGAAATAGTGTCGCAGAAATAAAGACAGAATATGGAAGGAGACAGGATTGCTGACTAATCTCATATGTACAGGGAGAACGACACTCCATGCAGCTTAGCTCCAACATGTGAGCGTGGGACAGAAAAGCAAGGTGAACCTAAAGACATCCCATGGACACACTGAGCTGGAACCAACTCTGCCCATAGGTGGTGGGGCCAGGTTCAGATGCTTGCAGTAACCGCATCCTCCTGTGAATCTGGGTCTACATGGCTGTGTCTCCCTGGGGGCTACCCACACTGTGGATTCCACAGGTGGAGGTGACCTTCTTGGGCACTGCTGGGACACTTCCTGGGCCTGCCTGGGCAGTGGTAGGGCTCAGAGAACTTCAGCGTTAGGGCCTTGGGGAGTCTATGTCAGACTTGAGGAC,AATACAATGTTCTCCAGAAATAGTGTCGCAGAAATAAAGACAGAATATGGAAGGAGACAGGATTGCTGACTAATCTCATATGTACAGGGAGAACGACACTCCATGCAGCTTAGCTCCAACATGTGAGCGTGGGACAGAAAAGCAAGGTGAACCTAAAGACATCCCATGGACACACTGAGCTGGAACCAACTCTGCCCATAGATGGTGGGGCCAGGTTCAGATGCTTGCAGTAACCGCATCCTCCTGTGAATCTGGGTCTACATGGCTGTGGCTCCCTGGGGGCTACCCACACTGTGGATTCCACAGGTGGAGGTGACCTTCTTGGGCACTGCTGGGACACTTCCTGGGCCTGCCTGGGCAGTGGTAGGGCTCAGAGAACTTCAGCGTTAGGGCCTTGGGGAGTCTATGTCAGACTTGAGGAC . PASS ID=chr1-811517-SNV-C-T:chr1-811733-SNV-C-T,chr1-811391-DEL-0-421,chr1-811660-SNV-G-T,chr1-811591-SNV-G-A
The ID field contains one ID per alternative allele. If an allele contains nested alleles, its ID is composed of a sequence of IDs of the lowest level alleles, separated by “:” (see first ALT allele in example above)
The IDs itself are unique, for HGSVC we defined them based on the following pattern: ---- (for SNV only) ---- (for other variant types: INS, DEL, COMPLEX)
Note: for variants != SNVs, the field is needed to make sure IDs are unique in case there are multiple alleles with the same length at the same location.
Biallelic (separate record for each alternative allele) If an alternative allele is composed of multiple IDs (see above), there is a record for each corresponding alternative allele (see below)
chr1 811390 . AATACAATGTTCTCCAGAAATAGTGTCGCAGAAATAAAGACAGAATATGGAAGGAGACAGGATTGCTGACTAATCTCATATGTACAGGGAGAACGACACTCCATGCAGCTTAGCTCCAACATGTGAGCGTGGGACAGAAAAGCAAGGTGAACCTAAAGACATCCCATGGACACACTGAGCTGGAACCAACTCTGCCCATAGGTGGTGGGGCCAGGTTCAGATGCTTGCAGTAACCGCATCCTCCTGTGAATCTGGGTCTACATGGCTGTGGCTCCCTGGGGGCTACCCACACTGTGGATTCCACAGGTGGAGGTGACCTTCTTGGGCACTGCTGGGACACTTCCTGGGCCTGCCTGGGCAGTGGTAGGGCTCAGAGAACTTCAGCGTTAGGGCCTTGGGGAGTCTATGTCAGACTTGAGGAC A . . ID=chr1-811391-DEL-0-421
chr1 811517 . C T . . ID=chr1-811517-SNV-C-T
chr1 811591 . G A . . ID=chr1-811591-SNV-G-A
chr1 811660 . G T . . ID=chr1-811660-SNV-G-T
chr1 811733 . C T . . ID=chr1-811733-SNV-C-T
This biallelic representation contains the same information, just in a different representation. It can be used for evaluation and comparison to external truth sets.
Download
git clone https://github.com/glennhickey/resolve-nested-genotypes.git
cd resolve-nested-genotypes
Build with Rust
cargo build --release
target/release/resolve-nested-genotypes <deconstructed VCF> <genotyped VCF> > out.vcf
Note that sites in the <genotyped VCF> must have the exact same alleles in the exact same order as sites in the deconstructed VCF. Only the coordinates are used to map between the two files, so inconsistencies may not be caught. <genotyped VCF> does not need the same IDs or INFO fields.
Author: Glenn Hickey
Licence: MIT