Learning representations of chromatin contacts using a recurrent neural network identifies genomic drivers of conformation.

Despite the availability of chromatin conformation capture experiments, discerning the relationship between the 1D genome and 3D conformation remains a challenge, which limits our understanding of their affect on gene expression and disease. We propose Hi-C-LSTM, a method that produces low-dimensional latent representations that summarize intra-chromosomal Hi-C contacts via a recurrent long short-term memory neural network model. We find that these representations contain all the information needed to recreate the observed Hi-C matrix with high accuracy, outperforming existing methods. These representations enable the identification of a variety of conformation-defining genomic elements, including nuclear compartments and conformation-related transcription factors. They furthermore enable in-silico perturbation experiments that measure the influence of cis-regulatory elements on conformation.

Latent Representation of the Human Pan-Celltype Epigenome Through a Deep Recurrent Neural Network.

The availability of thousands of assays of epigenetic activity necessitates compressed representations of these data sets that summarize the epigenetic landscape of the genome. Until recently, most such representations were cell type-specific, applying to a single tissue or cell state. Recently, neural networks have made it possible to summarize data across tissues to produce a pan-cell type representation. In this work, we propose Epi-LSTM, a deep long short-term memory (LSTM) recurrent neural network autoencoder to capture the long-term dependencies in the epigenomic data. The latent representations from Epi-LSTM capture a variety of genomic phenomena, including gene-expression, promoter-enhancer interactions, replication timing, frequently interacting regions, and evolutionary conservation. These representations outperform existing methods in a majority of cell types while yielding smoother representations along the genomic axis due to their sequential nature.