In the past six years worldwide capacity for human genome sequencing has grown by more than five orders of magnitude, with costs falling by nearly two orders of magnitude over the same period [1], [2]. The rapid expansion in the production of next-generation sequence data and the use of these data in a wide range of new applications has created a need for improved computational tools for data processing. The Sentieon Genomics tools provide an optimized reimplementation of the most accurate pipelines for calling variants from next-generation sequence data, resulting in more than a 10-fold increase in processing speed while providing identical results to best practices pipelines. Here we demonstrate the consistency and improved performance of Sentieon's tools relative to BWA, GATK, MuTect, and MuTect2 through analysis of publicly available human exome, low-coverage genome, and high-depth genome sequence data.

Detection of somatic mutations in tumor samples is important in the clinic, where treatment decisions are increasingly based upon molecular diagnostics. However, accurate detection of these mutations is difficult, due in part to intra-tumor heterogeneity, contamination of the tumor sample with normal tissue and pervasive structural variation. Here, we describe Sentieon TNscope, a haplotype-based somatic variant caller with increased accuracy relative to existing methods. An early engineering version of TNscope was used in our submission to the most recent ICGC-DREAM Somatic Mutation calling challenge. In that challenge, TNscope is the leader in accuracy for SNVs, indels and SVs. To further improve variant calling accuracy, we combined the improvements in the variant caller with machine learning. We benchmarked TNscope using in-silico mixtures of well-characterized Genome in a Bottle (GIAB) samples. TNscope displays higher accuracy than the other benchmarked tools and the accuracy is substantially improved by the machine learning model.

Sentieon DNAseq Software is a suite of tools for running DNA sequencing secondary analyses. The Sentieon DNAseq Software produces identical results to the Genome Analysis Toolkit (GATK) Best Practice Workflow using HaplotypeCaller, with more than a 20-fold increase in processing speed on the same hardware. This paper presents a benchmark analysis of the GATK and Sentieon DNAseq software packages using publically available datasets from the 1000 genomes database, and includes speed comparisons and output concordance analyses.

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Sentieon DNA Software is a suite of tools that allow running DNA sequencing secondary analysis pipelines. The Sentieon DNA Software produces results identical to the Genome Analysis Toolkit (GATK) Best Practice Workflow using HaplotypeCaller, with more than 20x increase in processing speed on the same hardware. This paper presents a benchmark analysis of both speed comparison and output concordance between using GATK and Sentieon DNA software on publically available datasets from the 100 genomes database.