ChromaFold predicts the 3D contact map from single-cell chromatin accessibility Journal Article


Authors: Gao, V. R.; Yang, R.; Das, A.; Luo, R.; Luo, H.; McNally, D. R.; Karagiannidis, I.; Rivas, M. A.; Wang, Z. M.; Barisic, D.; Karbalayghareh, A.; Wong, W.; Zhan, Y. A.; Chin, C. R.; Noble, W. S.; Bilmes, J. A.; Apostolou, E.; Kharas, M. G.; Béguelin, W.; Viny, A. D.; Huangfu, D.; Rudensky, A. Y.; Melnick, A. M.; Leslie, C. S.
Article Title: ChromaFold predicts the 3D contact map from single-cell chromatin accessibility
Abstract: Identifying cell-type-specific 3D chromatin interactions between regulatory elements can help decipher gene regulation and interpret disease-associated non-coding variants. However, achieving this resolution with current 3D genomics technologies is often infeasible given limited input cell numbers. We therefore present ChromaFold, a deep learning model that predicts 3D contact maps, including regulatory interactions, from single-cell ATAC sequencing (scATAC-seq) data alone. ChromaFold uses pseudobulk chromatin accessibility, co-accessibility across metacells, and a CTCF motif track as inputs and employs a lightweight architecture to train on standard GPUs. Trained on paired scATAC-seq and Hi-C data in human samples, ChromaFold accurately predicts the 3D contact map and peak-level interactions across diverse human and mouse test cell types. Compared to leading contact map prediction models that use ATAC-seq and CTCF ChIP-seq, ChromaFold achieves state-of-the-art performance using only scATAC-seq. Finally, fine-tuning ChromaFold on paired scATAC-seq and Hi-C in a complex tissue enables deconvolution of chromatin interactions across cell subpopulations. © The Author(s) 2024.
Keywords: genetics; mouse; animal; metabolism; animals; mice; chromatin; genomics; rodent; cell; single cell analysis; single-cell analysis; procedures; machine learning; chromate; ccctc-binding factor; transcription factor ctcf; deconvolution; humans; human; deep learning; chromatin immunoprecipitation sequencing; three-dimensional modeling
Journal Title: Nature Communications
Volume: 15
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2024-11-01
Start Page: 9432
Language: English
DOI: 10.1038/s41467-024-53628-0
PUBMED: 39487131
PROVIDER: scopus
PMCID: PMC11530433
DOI/URL:
Notes: Article -- MSK corresponding author is Christina Leslie -- Erratum issued, see DOI: 10.1038/s41467-025-56017-3 -- Source: Scopus
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MSK Authors
  1. Rui Yang
    23 Yang
  2. Danwei Huangfu
    55 Huangfu
  3. Alexander Rudensky
    156 Rudensky
  4. Christina Leslie
    188 Leslie
  5. Michael Kharas
    96 Kharas
  6. Hanzhi Luo
    22 Luo
  7. Zhongmin Wang
    12 Wang
  8. Renhe Luo
    8 Luo
  9. Vianne Ran Gao
    12 Gao
  10. Yingqian Zhan
    36 Zhan
  11. Wilfred Wong
    6 Wong