GenPairX: A Hardware-Algorithm Co-Designed Accelerator for Paired-End Read Mapping

Genome sequencing has become a central focus in computational biology due to its critical role in applications such as personalized medicine, disease outbreak tracking, and evolutionary research. A genome study typically begins with sequencing, which produces millions to billions of short DNA fragments known as reads. Extracting meaningful biological insights from these reads requires a computationally intensive step called read mapping, where each read is aligned to a reference genome. Read mapping for short reads comes in two forms: single-end and paired-end, with the latter being more prevalent due to its higher accuracy and support for advanced analysis. Read mapping remains a major performance bottleneck in genome analysis as a result of the extensive use of computationally intensive dynamic programming. Prior efforts have attempted to mitigate this cost by employing filters to identify and potentially discard computationally expensive matches and leveraging hardware accelerators to speed up the computations. While partially effective, these approaches have limitations. In particular, existing filters are often ineffective for paired-end reads, as they evaluate each read independently and exhibit relatively low filtering ratios. In this work, we propose GenPairX, a hardware-algorithm codesigned accelerator that efficiently minimizes the computational load of paired-end read mapping while enhancing the throughput of memory-intensive operations. GenPairX introduces: (1) a novel filtering algorithm that jointly considers both reads in a pair to improve filtering effectiveness, and a lightweight alignment algorithm to replace most of the computationally expensive dynamic programming operations, and (2) two specialized hardware mechanisms to support the proposed algorithms. The proposed hardware addresses the high memory bandwidth demands of the read filtering process via orchestration of memory accesses over high-bandwidth memory channels, and accelerates the alignment of candidate reads via simple vectorized logical XOR operators. Our evaluations show that GenPairX delivers substantial performance improvements over state-of-the-art solutions, achieving$1575 \times$and$1.43 \times$higher throughput per watt compared to leading CPU-based and accelerator-based read mappers, respectively, all without compromising accuracy.