Parameterized syncmer schemes improve long-read mapping

Abhinav Dutta, David Pellow and Ron Shamir

PLOS Computational Biology, 2022, vol. 18, issue 10, 1-19

Abstract: Motivation: Sequencing long reads presents novel challenges to mapping. One such challenge is low sequence similarity between the reads and the reference, due to high sequencing error and mutation rates. This occurs, e.g., in a cancer tumor, or due to differences between strains of viruses or bacteria. A key idea in mapping algorithms is to sketch sequences with their minimizers. Recently, syncmers were introduced as an alternative sketching method that is more robust to mutations and sequencing errors. Results: We introduce parameterized syncmer schemes (PSS), a generalization of syncmers, and provide a theoretical analysis for multi-parameter schemes. By combining PSS with downsampling or minimizers we can achieve any desired compression and window guarantee. We implemented the use of PSS in the popular minimap2 and Winnowmap2 mappers. In tests on simulated and real long-read data from a variety of genomes, the PSS-based algorithms, with scheme parameters selected on the basis of our theoretical analysis, reduced unmapped reads by 20-60% at high compression while usually using less memory. The advantage was more pronounced at low sequence identity. At sequence identity of 75% and medium compression, PSS-minimap had only 37% as many unmapped reads, and 8% fewer of the reads that did map were incorrectly mapped. Even at lower compression and error rates, PSS-based mapping mapped more reads than the original minimizer-based mappers as well as mappers using the original syncmer schemes. We conclude that using PSS can improve mapping of long reads in a wide range of settings. Author summary: Popular long-read mappers use minimizers, the minimal hashed k-mers from overlapping windows, as alignment seeds. Recent work showed that syncmers, which select a fixed set of k-mers as seeds, are more likely to be conserved under errors or mutations than minimizers, making them potentially useful for mapping error-prone long reads. We introduce a framework for creating syncmers, that we call parameterized syncmer schemes, which generalize those introduced so far, and provide a theoretical analysis of their properties. We implemented parameterized syncmer schemes in the minimap2 and Winnowmap2 long-read mappers. Using parameters selected on the basis of our theoretical analysis we demonstrate improved mapping performance, with fewer unmapped and incorrectly mapped reads on a variety of simulated and real datasets. The improvements are consistent across a broad range of compression rates and sequence identities, with the most significant improvements for lower sequence identity (high error or mutation rates) and high compression.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pcbi00:1010638

DOI: 10.1371/journal.pcbi.1010638

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