VarBridge lifts variants from a source to a target genome using an alignment of the source to the target genome.

VarBridge can be built from source using a recursive clone and make. VarBridge depends on HTSlib and Boost.

git clone --recursive https://github.com/tobiasrausch/VarBridge.git

cd VarBridge/

make all

For a new telomere-to-telomere assembly (asm) and variants of a sample S1 against that assembly (asm.bcf) the lifting to GRCh38 requires an alignment of asm against GRCh38 (asm_to_hg38.bam), e.g.:

minimap2 -a -x asm5 --cs hg38.fa asm.fa | samtools sort -O bam -o asm_to_hg38.bam

With such an alignment, VarBridge lifts variants using:

varbridge lift -g hg38.fa -s S1 -a asm.bcf asm_to_hg38.bam

You can redirect the output to a VCF file and also output all non-liftable variants with their closest liftable position in GRCh38.

varbridge lift -g hg38.fa -b out.bed -o out.vcf -s S1 -a asm.bcf asm_to_hg38.bam

Please note that the output VCF is unsorted and thus, you need to sort it using bcftools for indexing.

bcftools sort out.vcf > sorted.vcf

Variants where the ALT allele in the assembly is the REF allele in the target genome (GRCh38) get the flag REF_ALT_SWAP. Please note that homozygous alternative variants on the assembly with a 1/1 genotype are then converted to 0/0 for the target genome if there is a REF_ALT_SWAP. You can use bcftools to filter such non-variant sites.

bcftools view --min-ac 1 sorted.vcf

VarBridge is free and open source (BSD). Consult the accompanying LICENSE file for more details.

HTSlib is heavily used for alignment processing. Boost for various data structures and algorithms and Edlib for alignments of the REF and ALT allele to the target genome.