RawHash: enabling fast and accurate real-time analysis of raw nanopore signals for large genomes.

Nanopore sequencers generate electrical raw signals in real-time while sequencing long genomic strands. These raw signals can be analyzed as they are generated, providing an opportunity for real-time genome analysis. An important feature of nanopore sequencing, Read Until, can eject strands from sequencers without fully sequencing them, which provides opportunities to computationally reduce the sequencing time and cost. However, existing works utilizing Read Until either (i) require powerful computational resources that may not be available for portable sequencers or (ii) lack scalability for large genomes, rendering them inaccurate or ineffective. We propose RawHash, the first mechanism that can accurately and efficiently perform real-time analysis of nanopore raw signals for large genomes using a hash-based similarity search. To enable this, RawHash ensures the signals corresponding to the same DNA content lead to the same hash value, regardless of the slight variations in these signals. RawHash achieves an accurate hash-based similarity search via an effective quantization of the raw signals such that signals corresponding to the same DNA content have the same quantized value and, subsequently, the same hash value. We evaluate RawHash on three applications: (i) read mapping, (ii) relative abundance estimation, and (iii) contamination analysis. Our evaluations show that RawHash is the only tool that can provide high accuracy and high throughput for analyzing large genomes in real-time. When compared to the state-of-the-art techniques, UNCALLED and Sigmap, RawHash provides (i) 25.8× and 3.4× better average throughput and (ii) significantly better accuracy for large genomes, respectively. Source code is available at https://github.com/CMU-SAFARI/RawHash.

From molecules to genomic variations: Accelerating genome analysis via intelligent algorithms and architectures.

We now need more than ever to make genome analysis more intelligent. We need to read, analyze, and interpret our genomes not only quickly, but also accurately and efficiently enough to scale the analysis to population level. There currently exist major computational bottlenecks and inefficiencies throughout the entire genome analysis pipeline, because state-of-the-art genome sequencing technologies are still not able to read a genome in its entirety. We describe the ongoing journey in significantly improving the performance, accuracy, and efficiency of genome analysis using intelligent algorithms and hardware architectures. We explain state-of-the-art algorithmic methods and hardware-based acceleration approaches for each step of the genome analysis pipeline and provide experimental evaluations. Algorithmic approaches exploit the structure of the genome as well as the structure of the underlying hardware. Hardware-based acceleration approaches exploit specialized microarchitectures or various execution paradigms (e.g., processing inside or near memory) along with algorithmic changes, leading to new hardware/software co-designed systems. We conclude with a foreshadowing of future challenges, benefits, and research directions triggered by the development of both very low cost yet highly error prone new sequencing technologies and specialized hardware chips for genomics. We hope that these efforts and the challenges we discuss provide a foundation for future work in making genome analysis more intelligent.