ZipHiC: a novel Bayesian framework to identify enriched interactions and experimental biases in Hi-C data.

Abstract

Several computational and statistical methods have been developed to analyze data generated through the 3C-based methods, especially the Hi-C. Most of the existing methods do not account for dependency in Hi-C data. Here, we present ZipHiC, a novel statistical method to explore Hi-C data focusing on the detection of enriched contacts. ZipHiC implements a Bayesian method based on a hidden Markov random field (HMRF) model and the Approximate Bayesian Computation (ABC) to detect interactions in two-dimensional space based on a Hi-C contact frequency matrix. ZipHiC uses data on the sources of biases related to the contact frequency matrix, allows borrowing information from neighbours using the Potts model and improves computation speed using the ABC model. In addition to outperforming existing tools on both simulated and real data, our model also provides insights into different sources of biases that affects Hi-C data. We show that some datasets display higher biases from DNA accessibility or Transposable Elements content. Furthermore, our analysis in Drosophila melanogaster showed that approximately half of the detected significant interactions connect promoters with other parts of the genome indicating a functional biological role. Finally, we found that the micro-C datasets display higher biases from DNA accessibility compared to a similar Hi-C experiment, but this can be corrected by ZipHiC. The R scripts are available at https://github.com/igosungithub/HMRFHiC.git. Supplementary data are available at Bioinformatics online.