Predicting Chromatin Interactions from DNA Sequence Using DeepC

Abstract

The genome 3D structure is central to understanding how disease-associated genetic variants in the noncoding genome regulate their target genes. Genome architecture spans large-scale structures determined by fine-grained regulatory elements, making it challenging to predict the effects of sequence and structural variants. Experimental approaches for chromatin interaction mapping remain costly and time-consuming, limiting their use for interrogating changes of chromatin architecture associated with genomic variation at scale. Computational models to predict chromatin interactions have either interpreted chromatin at coarse resolution or failed to capture the long-range dependencies of larger sequence contexts. To bridge this gap, we previously developed deepC, a deep neural network approach to predict chromatin interactions from DNA sequence at megabase scale. deepC employs dilated convolutional layers to achieve simultaneously a large sequence context while interpreting the DNA sequence at single base pair resolution. Using transfer learning of convolutional weights trained to predict a compendium of chromatin features across cell types allows deepC to predict cell type-specific chromatin interactions from DNA sequence alone. Here, we present a detailed workflow to predict chromatin interactions with deepC. We detail the necessary data pre-processing steps, guide through deepC model training, and demonstrate how to employ trained models to predict chromatin interactions and the effect of sequence variations on genome architecture.