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

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 <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://github.com/Humonex/HapBridge">https://github.com/Humonex/HapBridge</ext-link> .