PreprintCited by 21Genomics and Chromatin DynamicsProtein Structure and DynamicsGenomic variations and chromosomal abnormalities

HiC-GNN: A Generalizable Model for 3D Chromosome Reconstruction Using Graph Convolutional Neural Networks

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Van Hovenga, Oluwadare, Oluwatosin, Kalita, Jugal·2021·Computational and Structural Biotechnology Journal

Preprint — published as 10.1016/j.csbj.2022.12.051

Abstract

Chromosome conformation capture (3C) is a method of measuring chromosome topology in terms of loci interaction. The Hi-C method is a derivative of 3C that allows for genome wide quantification of chromosome interaction. From such interaction data, it is possible to infer the three-dimensional (3D) structure of the underlying chromosome. In this paper, we use a node embedding algorithm and a graph neural network to predict the 3D coordinates of each genomic loci from the corresponding Hi-C contact data. Unlike other chromosome structure prediction methods, our method can generalize a single model across Hi-C resolutions, multiple restriction enzymes, and multiple cell populations while maintaining reconstruction accuracy. We derive these results using three separate Hi-C data sets from the GM12878, GM06990, and K562 cell lines. We also compare the reconstruction accuracy of our method to four other existing methods and show that our method yields superior performance. Our algorithm outperforms the state-of-the-art methods in the accuracy of prediction and introduces a novel method for 3D structure prediction from Hi-C data. Author Summary: We developed a novel method, HiC-GNN, for predicting the three-dimensional structures of chromosomes from Hi-C data. HiC-GNN is unique from other methods for chromosome structure prediction in that it learns in an eager setting rather than a lazy setting. Thus, the models learned by HiC-GNN can be generalized to unseen data. To the authors’ knowledge, this generalizing capability is not present in any existing methods. We show that this generalization is robust to input resolution, restriction enzyme, and contact sparsity. We also show that our method outperforms existing methods using both generalized and non-generalized models. Moreover, we also show that our method is more robust to contact variance than the compared methods. Availability: All our source codes and data are available at https://github.com/OluwadareLab/HiC-GNN , and is made available as a containerized application that can be run on any platform.

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  • A mixed pooling multi-view self-attention autoencoder has generated patient representations for predicting a patient's risk of developing a disease in a future visit or the diagnostic codes of the next visit.

    “A mixed pooling multi-view self-attention autoencoder has generated patient representations for predicting either a patient’s risk of developing a disease in a future visit, or the diagnostic codes of the next visit [207].”

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Authors
Hovenga, V., Oluwadare, O., & Kalita, J.
Affiliations
University of Colorado Colorado Springs (US)
Corresponding author
Oluwadare, Oluwatosin
Venue
Computational and Structural Biotechnology Journal
Publisher
openRxiv
Published
2021-12-01
Volume
21
Pages
812-836
ISSN
2001-0370 (ISSN-L)
OpenAlex
W4313399484
Cited by
21
References
59
Citations by year
2026: 7 · 2025: 6 · 2024: 5 · 2023: 2 · 2022: 1
FWCI
1.14
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Computational and Structural Biotechnology Journal (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Science Foundation (2153205)
  • University of Colorado
  • University of Colorado Colorado Springs
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
Keywords
Hi-C, graph neural networks, chromosome conformation capture, contact maps, node embeddings, cross-dataset generalization, pre-trained models, restriction enzymes, cell populations

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