VEHiCLE: a Variationally Encoded Hi-C Loss Enhancement algorithm for improving and generating Hi-C data.

Chromatin conformation plays an important role in a variety of genomic processes. Hi-C is one of the most popular assays for inspecting chromatin conformation. However, the utility of Hi-C contact maps is bottlenecked by resolution. Here we present VEHiCLE, a deep learning algorithm for resolution enhancement of Hi-C contact data. VEHiCLE utilises a variational autoencoder and adversarial training strategy equipped with four loss functions (adversarial loss, variational loss, chromosome topology-inspired insulation loss, and mean square error loss) to enhance contact maps, making them more viable for downstream analysis. VEHiCLE expands previous efforts at Hi-C super resolution by providing novel insight into the biologically meaningful and human interpretable feature extraction. Using a deep variational autoencoder, VEHiCLE provides a user tunable, full generative model for generating synthetic Hi-C data while also providing state-of-the-art results in enhancement of Hi-C data across multiple metrics.