A Lightweight Framework For Chromatin Loop Detection at the Single‐Cell Level

Author:

Wang Fuzhou1ORCID,Alinejad‐Rokny Hamid2,Lin Jiecong34,Gao Tingxiao5,Chen Xingjian1,Zheng Zetian1,Meng Lingkuan1,Li Xiangtao6,Wong Ka‐Chun1

Affiliation:

1. Department of Computer Science City University of Hong Kong Kowloon Tong Hong Kong SAR

2. BioMedical Machine Learning Lab, Graduate School of Biomedical Engineering University of New South Wales Sydney 2052 Australia

3. Molecular Pathology Unit, Center for Cancer Research, Massachusetts General Hospital Department of Pathology Harvard Medical School Boston MA 02129 USA

4. Department of Computer Science The University of Hong Kong Pok Fu Lam Hong Kong SAR

5. Department of Medical Biophysics, Faculty of Medicine University of Toronto Toronto Ontario M5G1L7 Canada

6. School of Artificial Intelligence Jilin University Changchun 130012 China

Abstract

AbstractSingle‐cell Hi‐C (scHi‐C) has made it possible to analyze chromatin organization at the single‐cell level. However, scHi‐C experiments generate inherently sparse data, which poses a challenge for loop calling methods. The existing approach performs significance tests across the imputed dense contact maps, leading to substantial computational overhead and loss of information at the single‐cell level. To overcome this limitation, a lightweight framework called scGSLoop is proposed, which sets a new paradigm for scHi‐C loop calling by adapting the training and inferencing strategies of graph‐based deep learning to leverage the sequence features and 1D positional information of genomic loci. With this framework, sparsity is no longer a challenge, but rather an advantage that the model leverages to achieve unprecedented computational efficiency. Compared to existing methods, scGSLoop makes more accurate predictions and is able to identify more loops that have the potential to play regulatory roles in genome functioning. Moreover, scGSLoop preserves single‐cell information by identifying a distinct group of loops for each individual cell, which not only enables an understanding of the variability of chromatin looping states between cells, but also allows scGSLoop to be extended for the investigation of multi‐connected hubs and their underlying mechanisms.

Funder

National Natural Science Foundation of China

Shenzhen Research Institute, City University of Hong Kong

City University of Hong Kong

Publisher

Wiley

Subject

General Physics and Astronomy,General Engineering,Biochemistry, Genetics and Molecular Biology (miscellaneous),General Materials Science,General Chemical Engineering,Medicine (miscellaneous)

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