ChromPhaser: A HiFi Read Phasing Framework Integrating SNPmers and Hi-C Data

Assembling complex heterozygous genomes is hindered by highly similar allelic sequences and interchromosomal repeats, such as segmental duplications and rDNA arrays. Partitioning long HiFi reads by individual homologous chromosome can greatly reduce this complexity, yet efficient methods for chromosome-scale read phasing are lacking. Here we present ChromPhaser, a novel framework that integrates de novo SNPmer detection with Hi-C data to assign HiFi reads to both chromosome and haplotype bins. ChromPhaser enables accurate chromosome-level haplotype-aware phasing of HiFi reads for the first time, substantially improving the efficiency and precision of downstream haplotype-resolved analyses across human and diverse nonhuman genomes.