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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 isessential to utilize the unique features that nanopore sequencing provides,enabling the early stopping of the sequencing of a read or the entiresequencing run based on the analysis. The state-of-the-art mechanism, RawHash,offers the first hash-based efficient and accurate similarity identificationbetween raw signals and a reference genome by quickly matching their hashvalues. In this work, we introduce RawHash2, which provides major improvementsover RawHash, including a more sensitive chaining implementation, weightedmapping decisions, frequency filters to reduce ambiguous seed hits, minimizersfor hash-based sketching, and support for the R10.4 flow cell version andvarious data formats such as POD5. Compared to RawHash, RawHash2 providesbetter 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 athttps://github.com/CMU-SAFARI/RawHash. We also provide the scripts to fullyreproduce our results on our GitHub page.

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