What it does
Strelka2 is a fast and accurate small variant caller optimized for analysis of germline variation in small cohorts (Strelka Germline) and somatic variation in tumor/normal sample pairs (Strelka Somatic).
Strelka accepts input read mappings from BAM or CRAM files, and optionally candidate and/or forced-call alleles from VCF. It reports all small variant predictions in VCF 4.1 format. Germline variant reporting uses the gVCF conventions to represent both variant and reference call confidence. For best somatic indel performance, Strelka is designed to be run with the Manta structural variant and indel caller, which provides additional indel candidates up to a given maxiumum indel size (by default this is 49). By design, Manta and Strelka run together with default settings provide complete coverage over all indel sizes (in additional to all SVs and SNVs) for clinical somatic and germline analysis scenarios.
The germline caller employs an efficient tiered haplotype model to improve accuracy and provide read-backed phasing, adaptively selecting between assembly and a faster alignment-based haplotyping approach at each variant locus. The germline caller also analyzes input sequencing data using a mixture-model indel error estimation method to improve robustness to indel noise.
Input
Sequencing Data
The input sequencing reads are expected to come from a paired-end sequencing assay. Any input other than paired-end reads are ignored by default except to double-check for putative somatic variant evidence in the normal sample during somatic variant analysis. Read lengths above ~400 bases are not tested.
Alignment Files
All input sequencing reads should be mapped by an external tool and provided as input in BAM. or CRAM format.
The following limitations apply to the input BAM/CRAM alignment records:
VCF Files
Input VCF files are accepted for a number of roles as described below. All input VCF records are checked for compatibility with the given reference genome, in additional to role-specific checks described below. If any VCF record's REF field is not compatible with the reference genome a runtime error will be triggered. 'Compatible with the reference genome' means that each VCF record's REF base either (1) matches the corresponding reference genome base or the VCF record's REF base is 'N' or the reference genome base is any ambiguous IUPAC base code (all ambiguous base codes are converted to 'N' while importing the reference).
Output
Variants
This describes all potential variant loci across all samples. Note this file includes non-variant loci if they have a non-trivial level of variant evidence or contain one or more alleles for which genotyping has been forced. Please see the multi-sample variants VCF section below for additional details on interpreting this file.
Genome
This is the genome VCF output for sample N, which includes both variant records and compressed non-variant blocks. The sample index, N is 1-indexed and corresponds to the input order of alignment files on the configuration command-line.
References
More information are available on github.