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Abstract
Haplotype phase represents the collective genetic variation between homologous chromosomes and is an essential feature of non-haploid genomes. Here we describe a computational strategy to reliably determine complete whole-chromosome haplotypes using a combination of bulk long-range sequencing and Hi-C sequencing. We demonstrate that this strategy can resolve the haplotypes of parental chromosomes in diploid human genomes with high precision (>99%) and completeness (>98%) and assemble the syntenic structure of rearranged chromosomes in aneuploid cancer genomes at base pair level resolution. Our work enables direct interrogation of chromosome-specific alterations and chromatin reorganization using bulk DNA sequencing.
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