FiNGS: high quality somatic mutations using filters for next generation sequencing

Abstract

Background Somatic 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. Results Developed 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. Conclusions FiNGS 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.

A Functional Precision Medicine Pipeline Combines Comparative Transcriptomics and Tumor Organoid Modeling to Identify Bespoke Treatment Strategies for Glioblastoma

“…Reads were aligned to the reference genome GRCh37 using BWA-MEM and variants called using Strelka2 [ 17 , 18 ]. Variants were filtered using FiNGS and annotated using VEP [ 19 , 20 ]. Significantly mutated genes were determined using dNdSCV, with a significance threshold of q < 0.1 [ 21 ].…”

Genomic and Transcriptomic Profiling of Brain Metastases

“…Reads were aligned to the reference genome GRCh37 using BWA-MEM [ 29 ] and variants called using Strelka2 [ 30 ]. Variants were filtered using FiNGS [ 31 ] and annotated using VEP [ 32 ]. Significantly mutated genes were determined using dNdSCV [ 33 ].…”

Ventajas de la secuenciación de próxima generación sobre la hibridación fluorescente in situ para detectar la codeleción 1p/19q en oligodendrogliomas

“…Por ejemplo, una mutación presente en una fracción de las células cancerosas puede tener un rango de valores de VAF. Además, los cambios en el número de copias pueden afectar el VAF 63 .…”

“…Por otro lado, una VAF muy baja podría sugerir que solo está presente en una pequeña fracción de las células cancerosas. En general, esta información puede ayudar a dilucidar el papel que desempeña una variante en el desarrollo del cáncer 63 .…”