A 28nm Fully Integrated End-to-End Genome Analysis Accelerator for Next-Generation Sequencing

This paper presents the first end-to-end next-generation sequencing (NGS) data analysis accelerator for short-read mapping, haplotype calling, variant calling, and genotyping. It supports both single-end and paired-end short-reads (or reads) and uses the FM-index, a compact index data structure, for exact-match in short-read mapping. For inexact match part of short-read mapping, a dynamic programming array is proposed to determine the mapping results. To reduce the workload of short-read mapping, a rapid similarity calculation is designed. A rescue technique is also adopted to increase the overall sensitivity. In haplotype calling, a parallel $k$-mer processing engine can construct the de Bruijn graph and assemble the haplotypes. The variant calling step determines variants between a subject and a reference genome sequence with a variant discovery engine. Lastly, genotype likelihood is computed in parallel by a genotype likelihood computing engine, which outputs genotypes of all discovered variants and corresponding Phred-scaled likelihood (PL) values. This work completes end-to-end data analysis for the 50$\boldsymbol{\times}$ PrecisionFDA dataset in an average of 28.2 minutes. It achieves a 3-to-59$\boldsymbol{\times}$ higher throughput than the existing solutions with higher precision (99.79%) and sensitivity (99.03%). The chip also achieves a 935$\boldsymbol{\times}$ higher energy efficiency than the Illumina DRAGEN FPGA acceleration system.