4.8 Article

DeepLoop robustly maps chromatin interactions from sparse allele-resolved or single-cell Hi-C data at kilobase resolution

Journal

NATURE GENETICS
Volume 54, Issue 7, Pages 1013-+

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41588-022-01116-w

Keywords

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Funding

  1. National Institutes of Health [R01HG009658, R01DK113185]
  2. Mount Sinai Health Care Foundation [OSA510113, OSA510114]
  3. University of Miami [NIH U01AG072579]
  4. Cancer Data Sciences pilot grant from Case Comprehensive Cancer Center Support Grant [NIH P30CA043703]
  5. National Science Foundation [CCF-2006780, CCF-1815139]
  6. NIH training grant [T32HL007567]
  7. Callahan Foundation

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DeepLoop is a modular Hi-C processing workflow that enables robust chromatin interaction mapping from low-depth Hi-C data through deep-learning-based signal enhancement. It can identify allele-specific chromatin loops and structural variants, providing loop-resolution insights into the genetics of the three-dimensional genome.
DeepLoop is a modular Hi-C processing workflow that enables kilobase-resolution analysis of sparse data. Reanalysis of published data demonstrates that DeepLoop can identify allele-specific chromatin loops and large heterozygous structural variants. Mapping chromatin loops from noisy Hi-C heatmaps remains a major challenge. Here we present DeepLoop, which performs rigorous bias correction followed by deep-learning-based signal enhancement for robust chromatin interaction mapping from low-depth Hi-C data. DeepLoop enables loop-resolution, single-cell Hi-C analysis. It also achieves a cross-platform convergence between different Hi-C protocols and micrococcal nuclease (micro-C). DeepLoop allowed us to map the genetic and epigenetic determinants of allele-specific chromatin interactions in the human genome. We nominate new loci with allele-specific interactions governed by imprinting or allelic DNA methylation. We also discovered that, in the inactivated X chromosome (X-i), local loops at the DXZ4 'megadomain' boundary escape X-inactivation but the FIRRE 'superloop' locus does not. Importantly, DeepLoop can pinpoint heterozygous single-nucleotide polymorphisms and large structure variants that cause allelic chromatin loops, many of which rewire enhancers with transcription consequences. Taken together, DeepLoop expands the use of Hi-C to provide loop-resolution insights into the genetics of the three-dimensional genome.

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