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
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.
