Germline CNV Calling ASCN (WGS)
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The Germline WGS CNV caller (with Allele-Specific CN support) leverages depth of coverage and B-allele frequencies (BAFs) to detect germline copy number aberrations and regions with absence of heterozygosity (AOH).
The caller requires in input the sample to analyze and a catalog of population SNPs (used to estimate the B-allele frequencies across the genome). The output file is a VCF file. Several components of other germline CNV callers are reused, such as and counts estimation, correction, and . More details on the sample model selection are available in the section. See for more details on output files.
When enabled (default true), the caller can output an additional VCF with calls at resolutions compatible with cytogenetics technologies (e.g., ≥ 1 Mb, or whole-arm/whole-chromosome calls) For more information, see .
You can use the following command-line options:
--fastq-file1
,--fastq-file2
,--bam-input
, --cram-input
Specify an input file.
--cnv-population-b-allele-vcf
--enable-cnv
Enable or disable CNV processing. Set to true to enable CNV processing.
--enable-map-align
Enables the mapper and aligner module.
--output-directory
Output directory where all results are stored.
--output-file-prefix
Output file prefix that will be prepended to all result file names.
--ref-dir
The DRAGEN reference genome hashtable directory.
--sample-sex
If known, specify the sex of the sample. If the sample sex is not specified, the caller attempts to estimate the sample sex from alignments.
--cnv-enable-mosaic-calling
--cnv-enable-cyto-output
--cnv-enable-legacy-vcf-format
Use VCF v4.2 for CNV VCF output (default false).
--cnv-enable-self-normalization
Use self-normalization to normalize input sample.
The following is an example command line:
Whereas both the depth-only caller and the ASCN caller make use of a depth of coverage profile, the ASCN caller (but not the depth-only caller) additionally makes use of allelic read counts at sites along the genome provided through a population SNP catalog.
The ASCN caller segments both profiles (depth and BAF), then integrates their results. The depth-only caller only segments the depth profile.
The ASCN caller estimates the most likely diploid coverage for the input sample using both profiles (depth and BAF), while the depth-only caller has only the depth profile at its disposal.
The ASCN caller can also detect AOH/LOH regions and mosaic alterations, while the depth-only caller is limited to DEL and DUP regions.
Briefly, the following table summarizes the above differences:
Coverage Depth Profile
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B-Allele Frequency Profile
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Coverage Depth Segmentation
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B-Allele Frequency Segmentation
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DEL/DUP Detection
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Whole-arm/-chromosome Aneuploidy Detection
âś“ (Requires Cytogenetics Modality)
Whole-Genome Trisomy Detection
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Minor-Allele Copy-Number Estimation
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AOH/LOH Detection
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Mosaic Alterations Detection
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The following features available in the non-ASCN germline caller are not yet supported:
Pedigree mode
Exome support
Star-Allele caller integration
Segmental Duplications extension
Specify a population SNP catalog. For more information on specifying b-allele loci, see .
Enable MOSAIC-calling mode (default true). For more information, see .
Enable Cytogenetics-compatible output (default true). For more information, see .
The Germline WGS ASCN caller differs from the in various respects: