ArticleNature communications2026
HaploC-tools reveal haplotype-specific chromosome conformation and chromatin states.
Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
The sequences of homologous chromosomes differ in the presence of heterozygous single nucleotide polymorphisms (SNPs). Whether these differences translate into "heterozygous" chromatin three-dimensional structures is still largely unexplored. Here, we design HaploC-tools to optimize whole-chromosome phasing from high-throughput chromosome conformation capture (Hi-C) data and introduce tailored approaches to infer haplotype-specific copy number variants, boundary insulation, and chromatin compartmentalization. We use Haplo-C tools to analyze > 100 Hi-C dataset, including normal and cancer cell models, representing a unique resource to explore haplotype-specific chromatin conformation. Leveraging this dataset, we show that SNPs at CTCF binding sites lead to significantly different contact insulation between homologous chromosomes and discover widespread haplotype-specific compartments in cancer, driven by asymmetric loss of H3K9me3. These results implicate haplotype-specific chromatin configuration as a potential new mechanism of phenotypic reprogramming in disease emergence and progression.
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