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bioRxiv · 10.1101/2025.11.07.687303

HapBridge: A Methylation-Guided Approach for Correcting Switch Errors and Bridging Phased Blocks in Long-Read Phasing

Chen, H.·Nie, F.·Long, F.·Wang, J.
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Abstract

Long-read sequencing has substantially advanced haplotype phasing yet continues to face challenges in low-heterozygosity regions and switch errors caused by read noise. DNA methylation exhibits haplotype-specific patterns, providing complementary linkage information, but existing phasing algorithms have not fully leveraged these signals owing to their variability. Here, we present Hap-Bridge, a methylation-guided phasing framework that enhances single-nucleotide variant (SNV)-based phasing by detecting and correcting switch errors and bridging adjacent phased blocks. Evaluations on Oxford Nanopore R9/R10 and PacBio HiFi datasets show that HapBridge reduces switch errors by 3.07-18.72% and improves N50 length by 5.84-68.61% compared with Meth-Phaser, achieving higher phasing accuracy and contiguity. These results demonstrate that integrating methylation with sequence variation can provide a robust and intrinsic linkage signal that effectively improves haplotype continuity in long-read sequencing. HapBridge is publicly available at GitHub https://github.com/Humonex/HapBridge.

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Chen, H., Nie, F., Long, F., Wang, J.. 2025-11-10. HapBridge: A Methylation-Guided Approach for Correcting Switch Errors and Bridging Phased Blocks in Long-Read Phasing. https://doi.org/10.1101/2025.11.07.687303

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