Abstract
Chromosome conformation capture methods are being increasingly used to study three-dimensional genome architecture in multiple cell types and species. An important challenge is to examine changes in three-dimensional architecture across cell types and species. We present Arboretum-Hi-C, a multi-task spectral clustering method, to identify common and context-specific aspects of genome architecture. Compared to standard clustering, Arboretum-Hi-C produced more biologically consistent patterns of conservation. Most clusters are conserved and enriched for either high- or low-activity genomic signals. Most genomic regions diverge between clusters with similar chromatin state except for a few that are associated with lamina-associated domains and open chromatin.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-016-0962-8) contains supplementary material, which is available to authorized users.
Highlights
The three-dimensional (3D) organization of the genome is emerging as an important layer in the regulation of gene expression [1,2,3,4,5,6,7,8,9,10]
Our results indicate that most regions maintain their chromosome contact preferences between cell lines, and regions that diverge between species and cell lines are enriched for lamina-associated domains (LADs) and architectural proteins
We evaluated the quality of clusters from each clustering method using five different statistical measures: (1) the Davies–Bouldin index (DBI), (2) the silhouette index (SI), (3) the difference in contact counts between regions in the same cluster and between regions from different clusters, (4) the number of clusters enriched for a regulatory signal, and (5) analysis of variance (ANOVA) of a regulatory signal
Summary
The three-dimensional (3D) organization of the genome is emerging as an important layer in the regulation of gene expression [1,2,3,4,5,6,7,8,9,10]. Genome-wide 3C data sets are becoming increasingly available for multiple species and tissues and have enabled us to examine the folding and organizational principles of the genome and identify longrange interactions among genomic loci [1, 11]. Studies in yeast have shown that such long-range interactions are enriched for loci involving tRNA genes, centromeres, early origins of replication [4], and transcription factories for regulation of gene expression [12]. In mammalian systems, such interactions are organized into architectural units known as compartments and. The second and third eigenvectors exhibited variation along the chromosomal arms, with increased magnitude in the centromeric and telomeric regions for the second and third eigenvectors, respectively
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