CatLearning: highly accurate gene expression prediction from histone mark

Author:

Lu Weining1,Tang Yin2,Liu Yu3,Lin Shiyi3,Shuai Qifan4,Liang Bin5,Zhang Rongqing6ORCID,Cheng Yu7,Fang Dong38ORCID

Affiliation:

1. Tsinghua University Beijing National Research Center for Information Science and Technology, , FIT Building, Haidian District, Beijing 100084, China

2. Zhejiang University Liangzhu Laboratory, , 1369 Wenyixi Road, Yuhang District, Hangzhou, Zhejiang, 311121, China

3. Zhejiang University Life Sciences Institute, , 866 Yuhangtang Road, Xihu District, Hangzhou, Zhejiang, 310058, China

4. Southeast University Chengxian College School of Electron and Computer, , 371 Heyan Road, Qixia District, Nanjing, Jiangsu 210088, China

5. Tsinghua University Department of Automation, , 1 Tsinghua Garden, Haidian District, Beijing, 100084, China

6. Yangtze Delta Region Institute of Tsinghua University Zhejiang Provincial Key Laboratory of Applied Enzymology, , 705 Yatai Road, Jiaxing 314006, China

7. The Chinese University of Hong Kong , Shatin, NT, Hong Kong, 999077, China

8. The Second Affiliated Hospital, Zhejiang University School of Medicine Department of Medical Oncology, , Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, 88 Jiefang Road, Shangcheng District, Hangzhou, Zhejiang, 310009, China

Abstract

Abstract Histone modifications, known as histone marks, are pivotal in regulating gene expression within cells. The vast array of potential combinations of histone marks presents a considerable challenge in decoding the regulatory mechanisms solely through biological experimental approaches. To overcome this challenge, we have developed a method called CatLearning. It utilizes a modified convolutional neural network architecture with a specialized adaptation Residual Network to quantitatively interpret histone marks and predict gene expression. This architecture integrates long-range histone information up to 500Kb and learns chromatin interaction features without 3D information. By using only one histone mark, CatLearning achieves a high level of accuracy. Furthermore, CatLearning predicts gene expression by simulating changes in histone modifications at enhancers and throughout the genome. These findings help comprehend the architecture of histone marks and develop diagnostic and therapeutic targets for diseases with epigenetic changes.

Funder

Opening Research Fund from Shanghai Key Laboratory of Stomatology, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine

Zhejiang Provincial Natural Science Foundation of China

Fundamental Research Funds for the Central Universities

National Natural Science Foundation of China

National Key R&D Program of China

Publisher

Oxford University Press (OUP)

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