Sentieon Segdup Gene Caller

Segdup Gene caller is a variant caller for genes located in segmental duplication regions that contain highly similar homologs or pseudogenes. It can leverage available long-read sequencing data to improve variant calling accuracy.

Segdup caller currently supports whole-genome sequencing (WGS) paired-end short reads of 150 bp length, such as those from Illumina, Element Biosciences, MGI, and others. Sentieon provides platform-specific short-read variant calling models. For accurate copy number calling and phasing, Segdup caller recommends a minimum of 20× coverage, with 30× being ideal.

Segdup caller supports additional long-read data from PacBio HiFi or Oxford Nanopore, aligned BAM files, using the corresponding Sentieon models.

Supported Genes

Segdup caller currently supports the following genes and segmental duplication regions:

Region Name	Genes Encoded
SMN1	SMN1, SMN2
PMS2	PMS2, PMS2CL
CYP2D6	CYP2D6, CYP2D7
GBA	GBA1, GBAP1
STRC	STRC, STRCP1
NCF1	NCF1, NCF1B
CFH	CFH, CFHR1, CFHR2, CFHR3, CFHR4
CYP11B1	CYP11B1, CYP11B2

Note: Segdup caller is expanding the list of supported genes. If there are particular genes you hope to support, or you encounter any issues, please file an issue.

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Installation

To install the package from Git:

git clone https://github.com/Sentieon/segdup-caller.git
pip install ./segdup-caller

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Dependencies

• Sentieon Genomics software (version 202503 or later)
• samtools (version 1.16 or later)
• bcftools (version 1.10 or later)

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Sentieon Models

You can find a list of Sentieon models in our Sentieon models repository.

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Usage

usage: segdup-caller [-h] --short SHORT [--long LONG] --sr_model SR_MODEL
                  [--lr_model LR_MODEL] --reference REFERENCE --genes GENES
                  [--sample_name SAMPLE_NAME] [--sr_prefix SR_PREFIX]
                  [--lr_prefix LR_PREFIX] --outdir OUTDIR

Targeted variant caller for genes with highly similar paralogs.

Options:

  -h, --help                Show this help message and exit

  --short SHORT, -s SHORT  Input short-read BAM or CRAM (required)

  --long LONG, -l LONG     Input long-read BAM or CRAM (optional)

  --sr_model SR_MODEL      Short-read model bundle (required)

  --lr_model LR_MODEL      Long-read model bundle (required if --long is provided)

  --reference REFERENCE, -r REFERENCE
                           Reference FASTA file

  --genes GENES, -g GENES  Comma-separated list of regions to be called.
                           Supported: CFH, CFHR3, CYP11B1, CYP2D6, GBA,
                           NCF1, PMS2, SMN1, STRC

  --sample_name SAMPLE_NAME
                           Sample name (default: use SM tag from the short-read BAM file)

  --sr_prefix SR_PREFIX    Output prefix for short-read results

  --lr_prefix LR_PREFIX    Output prefix for long-read results

  --outdir OUTDIR, -o OUTDIR
                           Output directory

Example

Calling SMN1/SMN2 with a short-read input bam:

segdup-caller -s $short_read_bam -r $hg38_REF --sr_model $short_read_model_bundle -g SMN1 -o $outdir 

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Output

Sentieon Segdup caller produces the following output:

• VCF files containing variant calls for each specified gene region
• A YAML file containing additional information, such as copy number states