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 |
13 Dec 1, 2022
27 Oct 22, 2022
889 Jan 1, 2023
14 Oct 14, 2022
1 Nov 2, 2021
18 Jul 23, 2022
2 Aug 6, 2021
8 Nov 4, 2022
88 Dec 16, 2022
25 Aug 20, 2022
22 Nov 27, 2022
7 Dec 20, 2022
82 Dec 20, 2022
7 Oct 20, 2022
3 Oct 09, 2022
1 Jan 15, 2022
1 Feb 15, 2022
219 Dec 21, 2022
1 Sep 08, 2021
1 Oct 01, 2022
18.6k Jan 02, 2023
2 Oct 08, 2021
125 Dec 21, 2022
2 Nov 07, 2022
22 Oct 26, 2022
7 Jan 09, 2022
1 Dec 16, 2021
52 Mar 15, 2022
31 Jul 13, 2022