Journal Article

Long-read mapping to repetitive reference sequences using Winnowmap2

Hansen, Nancy F., Phillippy, Adam M., Koren, Sergey, Rhie, Arang, Jain, Chirag

2022

Overview

Approximately 5–10% of the human genome remains inaccessible due to the presence of repetitive sequences such as segmental duplications and tandem repeat arrays. We show that existing long-read mappers often yield incorrect alignments and variant calls within long, near-identical repeats, as they remain vulnerable to allelic bias. In the presence of a nonreference allele within a repeat, a read sampled from that region could be mapped to an incorrect repeat copy. To address this limitation, we developed a new long-read mapping method, Winnowmap2, by using minimal confidently alignable substrings. Winnowmap2 computes each read mapping through a collection of confident subalignments. This approach is more tolerant of structural variation and more sensitive to paralog-specific variants within repeats. Our experiments highlight that Winnowmap2 successfully addresses the issue of allelic bias, enabling more accurate downstream variant calls in repetitive sequences. Winnowmap2 enables better long-read mapping and more accurate variant calling in repetitive regions of the genome.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/114/2785 / 631/1647/794 / 631/208/212 / Alleles / Bias / Bioinformatics / Biological Microscopy / Biological Techniques / Biomedical and Life Sciences / Biomedical Engineering/Biotechnology / Gene mapping / Genome, Human / Genomes / Humans / Life Sciences / Mapping / Nucleotide sequence / Proteomics / Repetitive Sequences, Nucleic Acid - genetics / Segmental Duplications, Genomic / Sequence Analysis, DNA / Tandem Repeat Sequences