RawHash2: Accurate and Fast Mapping of Raw Nanopore Signals using a Hash-based Seeding Mechanism

Summary: Raw nanopore signals can be analyzed while they are being generated, a process known as real-time analysis. Real-time analysis of raw signals is essential to utilize the unique features that nanopore sequencing provides, enabling the early stopping of the sequencing of a read or the entire sequencing run based on the analysis. The state-of-the-art mechanism, RawHash, offers the first hash-based efficient and accurate similarity identification between raw signals and a reference genome by quickly matching their hash values. In this work, we introduce RawHash2, which provides major improvements over RawHash, including a more sensitive chaining implementation, weighted mapping decisions, frequency filters to reduce ambiguous seed hits, minimizers for hash-based sketching, and support for the R10.4 flow cell version and various data formats such as POD5. Compared to RawHash, RawHash2 provides better F1 accuracy (on average by 3.44% and up to 10.32%) and better throughput (on average by 2.3x and up to 5.4x) than RawHash. Availability and Implementation: RawHash2 is available at https://github.com/CMU-SAFARI/RawHash. We also provide the scripts to fully reproduce our results on our GitHub page.