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

Nat Commun. 2022 Jun 28;13(1):3704. doi: 10.1038/s41467-022-31337-w.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatin* / genetics
  • Genomics*
  • Learning
  • Molecular Conformation
  • Neural Networks, Computer

Substances

  • Chromatin