Cited by 148Genomic variations and chromosomal abnormalitiesGenomics and Chromatin DynamicsGenome Rearrangement Algorithms

EagleC: A deep-learning framework for detecting a full range of structural variations from bulk and single-cell contact maps

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Wang, Xiaotao, Luan, Yu, Yue, Feng·2022·Science Advances

Abstract

The Hi-C technique has been shown to be a promising method to detect structural variations (SVs) in human genomes. However, algorithms that can use Hi-C data for a full-range SV detection have been severely lacking. Current methods can only identify interchromosomal translocations and long-range intrachromosomal SVs (>1 Mb) at less-than-optimal resolution. Therefore, we develop EagleC, a framework that combines deep-learning and ensemble-learning strategies to predict a full range of SVs at high resolution. We show that EagleC can uniquely capture a set of fusion genes that are missed by whole-genome sequencing or nanopore. Furthermore, EagleC also effectively captures SVs in other chromatin interaction platforms, such as HiChIP, Chromatin interaction analysis with paired-end tag sequencing (ChIA-PET), and capture Hi-C. We apply EagleC in more than 100 cancer cell lines and primary tumors and identify a valuable set of high-quality SVs. Last, we demonstrate that EagleC can be applied to single-cell Hi-C and used to study the SV heterogeneity in primary tumors.

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Authors
Wang, X., Luan, Y., & Yue, F.
Affiliations
Northwestern University (US)
Corresponding author
Yue, Feng
Venue
Science Advances
Published
2022-06-17
Volume
8
Issue
24
Pages
eabn9215-eabn9215
ISSN
2375-2548 (ISSN-L)
OpenAlex
W4282929864
Cited by
148
References
60
Citations by year
2026: 16 · 2025: 20 · 2024: 36 · 2023: 73 · 2022: 3
FWCI
19.91
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Science Advances (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
  • National Human Genome Research Institute (R01HG011207, R01HG009906, U24HG012070)
  • National Institute of General Medical Sciences (R35GM124820)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genome Rearrangement Algorithms
Keywords
structural variant calling, Hi-C, contact maps, deep learning, ensemble learning, fusion genes, chromatin interactions, single-cell Hi-C, cancer genome, HiChIP, ChIA-PET, Capture Hi-C

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