Quantification of DNA Cleavage Specificity in Hi-C Experiments

Hi-C experiments [1] produce large sets of DNA sequence read pairs, which are typically analyzed to deduce interactions across different loci within whole genomes. Here we show that the same read pairs can also be analyzed to characterize a key step in Hi-C experiments, the digestion of cross-linked chromatin with a restriction endonuclease. Specifically, we describe a computational method to estimate, directly from Hi-C reads, the fractions of cleavages resulting from random breakage and star activity. We have validated this method using Hi-C fragments from computer simulations, and its application to experimental Hi-C data sets reveals significantly different patterns of cleavage across different cell types. Knowledge of cleavage fractions will enable researchers to optimize Hi-C experimental conditions, develop accurate Hi-C simulations for testing computational algorithms, increase the number of interactions deducible from each Hi-C data set, and investigate biophysical properties that correlate with patterns of DNA cleavage.

[1] Lieberman-Aiden et al., Science 2009, 326, 289-293