Gauchian: WGS-based GBA variant caller

Gauchian is a targeted variant caller for the GBA gene based on a whole-genome sequencing (WGS) BAM file. Gauchian uses a novel method to solve the problems caused by the high sequence similarity with the pseudogene paralog GBAP1 and is able to detect variants accurately in the Exons 9-11 homology region, such as large deletions or duplications between GBA and GBAP1, and GBAP1-like variants in GBA, including p.A495P, p.L483P, p.D448H, c.1263del, RecNciI, RecTL and c.1263del+RecTL. In addition to these challenging variants, Gauchian also calls known pathogenic or likely pathogenic GBA variants classified in ClinVar. Please refer to our preprint for more details about the method.

Running the program

This Python3 program can be run as follows:

python -m gauchian --manifest MANIFEST_FILE \
                   --genome [19/37/38] \
                   --prefix OUTPUT_FILE_PREFIX \
                   --outDir OUTPUT_DIRECTORY \
                   --threads NUMBER_THREADS

The manifest is a text file in which each line should list the absolute path to an input BAM/CRAM file.
For CRAM input, it’s suggested to provide the path to the reference fasta file with --reference in the command.

Interpreting the output

The program produces a .tsv file in the directory specified by –outDir.
The fields are explained below:

Fields in tsv Explanation
Sample Sample name
is_biallelic_GBAP1-like_variant_exon9-11 Whether the sample is called as biallelic for GBAP1-like variants in exon9-11
is_carrier_GBAP1-like_variant_exon9-11 Whether the sample is called as a carrier for GBAP1-like variants in exon9-11
total_CN Total copy number of GBA+GBAP1
deletion_breakpoint_in_GBA_gene Whether the deletion breakpoint is in GBA gene if a deletion exists
GBAP1-like_variant_exon9-11 GBAP1-like variants called in exon9-11, two alleles separated by /
other_variants Other variants called (non-GBAP1-like variants or variants outside of exon9-11)

A .json file is also produced that contains more information about each sample.

Fields in json Explanation
Coverage_MAD Median absolute deviation of depth, measure of sample quality
Median_depth Sample median depth
deletion_CN CN of the unique region between GBA and GBAP1. This value plus 2 is the total CN
deletion_CN_raw Raw normalized depth of the unique region between GBA and GBAP1
variant_raw_count Supporting reads for each variant
snp_call GBA copy number call at GBA/GBAP1 differentiating sites
snp_raw Raw GBA copy number at GBA/GBAP1 differentiating sites
haplotypes Summary of haplotypes assembled across GBA/GBAP1 differentiating sites in Exon9-11


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