Deep learning-enhanced R-loop prediction provides mechanistic implications for repeat expansion diseases

Jiyun Hu; Zetong Xing; Hongbing Yang; Yongli Zhou; Liufei Guo; Xianhong Zhang; Longsheng Xu; Qiong Liu; Jing Ye; Xiaoming Zhong; Jixin Wang; Ruoyao Lin; Erping Long; Jiewei Jiang; Liang Chen; Yongcheng Pan; Lang He; Jia-Yu Chen

iScience (Aug 2024)

Deep learning-enhanced R-loop prediction provides mechanistic implications for repeat expansion diseases

Jiyun Hu,
Zetong Xing,
Hongbing Yang,
Yongli Zhou,
Liufei Guo,
Xianhong Zhang,
Longsheng Xu,
Qiong Liu,
Jing Ye,
Xiaoming Zhong,
Jixin Wang,
Ruoyao Lin,
Erping Long,
Jiewei Jiang,
Liang Chen,
Yongcheng Pan,
Lang He,
Jia-Yu Chen

Affiliations

Jiyun Hu: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Chemistry and Biomedicine Innovation Center (ChemBIC), Department of Neurology at Nanjing Drum Tower Hospital, Nanjing University, Nanjing, Jiangsu 210023, China
Zetong Xing: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Chemistry and Biomedicine Innovation Center (ChemBIC), Department of Neurology at Nanjing Drum Tower Hospital, Nanjing University, Nanjing, Jiangsu 210023, China
Hongbing Yang: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Chemistry and Biomedicine Innovation Center (ChemBIC), Department of Neurology at Nanjing Drum Tower Hospital, Nanjing University, Nanjing, Jiangsu 210023, China
Yongli Zhou: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Chemistry and Biomedicine Innovation Center (ChemBIC), Department of Neurology at Nanjing Drum Tower Hospital, Nanjing University, Nanjing, Jiangsu 210023, China
Liufei Guo: School of Computer Science and Technology, Xi’an University of Posts and Telecommunications, Xi’an, Shaanxi 710121, China
Xianhong Zhang: RNA Institute, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China
Longsheng Xu: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Chemistry and Biomedicine Innovation Center (ChemBIC), Department of Neurology at Nanjing Drum Tower Hospital, Nanjing University, Nanjing, Jiangsu 210023, China
Qiong Liu: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
Jing Ye: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Chemistry and Biomedicine Innovation Center (ChemBIC), Department of Neurology at Nanjing Drum Tower Hospital, Nanjing University, Nanjing, Jiangsu 210023, China
Xiaoming Zhong: Center of Excellence for Leukemia Studies, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
Jixin Wang: Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China
Ruoyao Lin: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Chemistry and Biomedicine Innovation Center (ChemBIC), Department of Neurology at Nanjing Drum Tower Hospital, Nanjing University, Nanjing, Jiangsu 210023, China
Erping Long: Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China
Jiewei Jiang: School of Electronic Engineering, Xi’an University of Posts and Telecommunications, Xi’an, Shaanxi 710121, China
Liang Chen: RNA Institute, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China
Yongcheng Pan: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
Lang He: School of Computer Science and Technology, Xi’an University of Posts and Telecommunications, Xi’an, Shaanxi 710121, China; Corresponding author
Jia-Yu Chen: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Chemistry and Biomedicine Innovation Center (ChemBIC), Department of Neurology at Nanjing Drum Tower Hospital, Nanjing University, Nanjing, Jiangsu 210023, China; Nanchuang (Jiangsu) Institute of Chemistry and Health, Nanjing, Jiangsu 210023, China; Corresponding author

Journal volume & issue: Vol. 27, no. 8
p. 110584

Abstract

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Summary: R-loops play diverse functional roles, but controversial genomic localization of R-loops have emerged from experimental approaches, posing significant challenges for R-loop research. The development and application of an accurate computational tool for studying human R-loops remains an unmet need. Here, we introduce DeepER, a deep learning-enhanced R-loop prediction tool. DeepER showcases outstanding performance compared to existing tools, facilitating accurate genome-wide annotation of R-loops and a deeper understanding of the position- and context-dependent effects of nucleotide composition on R-loop formation. DeepER also unveils a strong association between certain tandem repeats and R-loop formation, opening a new avenue for understanding the mechanisms underlying some repeat expansion diseases. To facilitate broader utilization, we have developed a user-friendly web server as an integral component of R-loopBase. We anticipate that DeepER will find extensive applications in the field of R-loop research.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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