Distance-based assessment of the localization of functional annotations in 3D genome reconstructions

摘要: Recent studies used the contact data or three-dimensional (3D) genome reconstructions from Hi-C (chromosome conformation capture with next-generation sequencing) to assess co-localization of functional genomic annotations in nucleus. These analyses dichotomized point pairs belonging a annotation as “close” “far” based on some threshold and then tested for enrichment pairs. We propose an alternative approach that avoids dichotomization instead directly estimates significance distances within 3D reconstruction. applied this Plasmodium falciparum, causative agent malaria, Saccharomyces cerevisiae compared results previous approaches. found significant centromeres, telomeres, virulence genes, several sets genes developmentally regulated expression P. falciparum; centromeres long terminal repeats S. cerevisiae. Additionally, we experimental observation telomeres form three seven clusters falciparum Applying affinity propagation clustering telomere coordinates yielded six both organisms. Distance-based assessment replicated key findings, while avoiding (which previously threshold-sensitive results).