Abstract
ObjectivesHi-C is a proximity-based ligation reaction used to detect regions of the genome that are close in 3D space (or “interacting”). Typically, results from Hi-C experiments (contact maps) are visualized as heatmaps or Circos plots. While informative, these visualizations do not directly represent genomic structure and folding, making the interpretation of the underlying 3D genomic organization obscured. Our objective was to generate a graph-based contact map representation that leads to a more intuitive structural visualization.ResultsNormalized contact maps were converted into undirected graphs where each vertex represented a genomic region and each edge represented a detected (intra- and inter-chromosomal) or known (linear) interaction between two regions. Each edge was weighted by the inverse of the linear distance (Hi-C experimental resolution) or the interaction frequency from the contact map. Graphs were generated based on this representation scheme for contact maps from existing fission yeast datasets. Originally, these datasets were used to (1) identify specific principles influencing fission yeast genome organization and (2) uncover changes in fission yeast genome organization during the cell cycle. When compared to the equivalent heatmaps and/or Circos plots, the graph-based visualizations more intuitively depicted the changes in genome organization described in the original studies.
Highlights
One of the major problems in the genomic era is understanding how genomes are organized and chromosomes are folded within cells
Each edge was weighted by the inverse of the linear distance (Hi-C experimental resolution) or the interaction frequency from the contact map
In addition to edges that represent the detected cis- and trans-interactions, we chose to include edges between each sequential genomic bin within a chromosome to better represent the linear extent of the genome
Summary
One of the major problems in the genomic era is understanding how genomes are organized and chromosomes are folded within cells. The close physical proximity of genetic elements located either distally on the same chromosome or located on different chromosomes, greatly impacts cellular processes such as transcription, replication and recombination [1]. Restriction enzyme digestion and ligation is preformed on the cross-linked regions to generate chromatin/DNA complexes which can be identified by high-throughput sequencing. The resultant sequence reads are mapped to a reference genome [8] to determine the frequency with which each interaction occurs within the population of cells. The results of a Hi-C experiment are often encoded as a symmetric N × N matrix (contact map) where N is the number of genomic “bins” into which the genome is partitioned. A Hi-C experiment in fission yeast that is able to attain 10 kB resolution will generate 1258 genomic bins, each representing roughly 10 kB of linear DNA sequence. Each cell (C Mi,j ) of the contact map records the interaction frequency between
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