Accelerated Systems for Portable DNA Sequencing

Abstract

The MinION is a revolutionary handheld DNA sequencer that is inexpensive, portable, and can perform real-time sequencing. MinION is increasingly used in Precision Medicine applications. However, the MinION lacks portable compute power. This thesis introduces two clinical applications of the MinION and identifies and solves performance bottlenecks through hardware and software solutions to enable portable microbial diagnostics. Finally, we discuss how our accelerated solutions will fit on a laptop with a GPU.

More than 99% of DNA fragments in a typical human sample are non-target (human), which may be skipped in real-time using the MinION’s Read Until feature. We analyze the performance of the Read Until pipeline in detecting target microbial species for targeted viral pathogen detection and microbiome abundance estimation. We find new sources of performance bottlenecks (basecaller in the classification of a fragment) that are not addressed by past genomics accelerators. While SquiggleFilter and DTWax are our solutions for targeted viral pathogen detection, RawMap is for untargeted microbiome analysis. We also discuss accelerating the bottleneck step in the DNA mapping software (Minimap2) used in all of MinION’s sequencing workflows.

For targeted virus detection, we discuss SquiggleFilter which is a portable and programmable hardware-software solution that directly analyzes MinION’s raw squiggles and filters everything except target viral DNA fragments. SquiggleFilter avoids the expensive basecalling step and uses hardware-accelerated subsequence Dynamic Time Warping (sDTW). We show that our 14.3W 13.25mm2 accelerator has 274× greater throughput and 3481× lower latency than existing GPU-based solutions while consuming half the power. DTWax overcomes the on-chip memory limitations of SquiggleFilter by optimizing its high-accuracy sDTW algorithm for GPUs resulting in a ∼1.92X sequencing speedup and ∼3.64X compute speedup: costup.

For the untargeted classification and analysis of microbiome, we discuss RawMap which is a machine-learning-based smart and efficient solution that reduces sequencing time and cost by ∼24% and computing cost by ∼22%. We also discuss how RawMap may be used as an alternative to the RT-PCR test for viral load quantification of SARS-CoV-2.

Minimap2 is a software used in all MinION workflows. minimap2-accelerated (mm2-ax) is a heterogeneous design for sequence mapping where minimap2’s bottleneck step is sped up on the GPU with bit-exact output. mm2-ax on an NVIDIA A100 GPU improves the bottleneck step (chaining) with 4.07 - 1.93X speedup: costup over a SIMD baseline.

Finally, we envision a portable solution to microbial diagnostics with a laptop connected to the MinION. DTWax can perform targeted virus detection on the GPU and RawMap does untargeted microbiome classification on the CPU. Post-sequencing tasks like basecalling, alignment (using mm2-ax) and variant calling use the GPU.