HiCPotts: An R/Bioconductor package to identify significant interactions in chromosome conformation capture data and model sources of biases.

Motivation: Chromosome Conformation Capture methods, including Hi-C, micro-C or Capture-C, are used to map chromatin interactions genome-wide. Most of the existing computational methods do not account for sources of biases (such as DNA accessibility, GC content or TE content) in the data. Results: We previously developed ZipHiC, a Bayesian method based on a the hidden Markov random field (HMRF) model and the Approximate Bayesian Computation (ABC), that uses zero-inflated Poisson distribution to model the noise, signal and false signal of the data and showed that this approach was able to detect biases from DNA accessibility, GC content and TE content in both Hi-C and micro-C data. Here, we present HiCPotts, another Bayesian method based on the HMRF model and the ABC that uses a zero-inflated Negative Binomial distribution instead to model the noise and signal of the data. We systematically show that HiCPotts reduces false positives and increases recovery of true interactions compared to ZipHiC, but also compared to other methods such as FastHiC, Juicer and HiCExplorer. Most importantly, we provide an R/Bioconductor package that allows modelling the noise, signal and false signal using various distributions such as the zero-inflated Negative Binomial (ZINB) and the zero-inflated Poisson distribution (ZIP). Availability: https://bioconductor.org/packages/HiCPotts/

Osuntoki, I. G., Harrison, A. P., Dai, H., Bao, Y., Zabet, N. R.

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