Abstract
BackgroundSomatic variant callers are used to find mutations in sequencing data from cancer samples. They are very sensitive and have high recall, but also may produce low precision data with a large proportion of false positives. Further ad hoc filtering is commonly performed after variant calling and before further analysis. Improving the filtering of somatic variants in a reproducible way represents an unmet need. We have developed Filters for Next Generation Sequencing (FiNGS), software written specifically to address these filtering issues.ResultsDeveloped and tested using publicly available sequencing data sets, we demonstrate that FiNGS reliably improves upon the precision of default variant caller outputs and performs better than other tools designed for the same task.ConclusionsFiNGS provides researchers with a tool to reproducibly filter somatic variants that is simple to both deploy and use, with filters and thresholds that are fully configurable by the user. It ingests and emits standard variant call format (VCF) files and will slot into existing sequencing pipelines. It allows users to develop and implement their own filtering strategies and simple sharing of these with others.
Highlights
Somatic variant callers are used to find mutations in sequencing data from cancer samples
Somatic variant callers find mutations in cancer samples by comparing sequencing data from matched tumor-normal sample pairs and they output lists of the differences they detect. These differences are a mixture of true somatic mutations and false positives. Confounding factors such as the purity of the samples, the sub-clonal heterogeneity of cancer samples, somatic copy number aberrations, artifacts introduced by sequencing chemistry, the alignment algorithm and the incomplete and repetitive nature of reference genomes all lead to somatic variant calls that are rich in false positives
The FiNGS default filters performed with both MuTect and Strelka2 calls, with a large increase in precision at the cost of a reduction in recall a b. These data demonstrate the value in further filtering variant calls beyond what is initially emitted by somatic variant callers
Summary
Somatic variant callers are used to find mutations in sequencing data from cancer samples. Background Somatic variant callers find mutations in cancer samples by comparing sequencing data from matched tumor-normal sample pairs and they output lists of the differences they detect. While this does output a standard VCF file, it only works with VCFs produced using the MuTect variant caller and requires users to fully commit to the GATK software ecosystem.
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