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|
|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|