Inferring CTCF-binding patterns and anchored loops across human tissues and cell types

Hang Xu; Xianfu Yi; Xutong Fan; Chengyue Wu; Wei Wang; Xinlei Chu; Shijie Zhang; Xiaobao Dong; Zhao Wang; Jianhua Wang; Yao Zhou; Ke Zhao; Hongcheng Yao; Nan Zheng; Junwen Wang; Yupeng Chen; Dariusz Plewczynski; Pak Chung Sham; Kexin Chen; Dandan Huang; Mulin Jun Li

doi:10.1016/j.patter.2023.100798

Inferring CTCF-binding patterns and anchored loops across human tissues and cell types

Patterns (N Y). 2023 Jul 12;4(8):100798. doi: 10.1016/j.patter.2023.100798. eCollection 2023 Aug 11.

Authors

Hang Xu^{1

2}, Xianfu Yi³, Xutong Fan³, Chengyue Wu⁴, Wei Wang¹, Xinlei Chu¹, Shijie Zhang⁵, Xiaobao Dong⁶, Zhao Wang⁵, Jianhua Wang³, Yao Zhou³, Ke Zhao⁵, Hongcheng Yao⁷, Nan Zheng⁸, Junwen Wang⁹, Yupeng Chen⁴, Dariusz Plewczynski¹⁰, Pak Chung Sham⁷, Kexin Chen¹, Dandan Huang¹¹, Mulin Jun Li^{1

3}

Affiliations

¹ Department of Epidemiology and Biostatistics, Key Laboratory of Prevention and Control of Human Major Diseases (Ministry of Education), National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin 300070, China.
² Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A∗STAR), Singapore 138648, Singapore.
³ Department of Bioinformatics, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
⁴ Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
⁵ Department of Pharmacology, Tianjin Key Laboratory of Inflammation Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
⁶ Department of Genetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
⁷ Centre for PanorOmic Sciences-Genomics and Bioinformatics Cores, The University of Hong Kong, Hong Kong 999077, China.
⁸ Department of Network Security and Informatization, Tianjin Medical University, Tianjin 300070, China.
⁹ Department of Health Sciences Research and Center for Individualized Medicine, Mayo Clinic, Scottsdale, AZ 85259, USA.
¹⁰ Faculty of Mathematics and Information Science, Warsaw University of Technology, Warsaw, Poland.
¹¹ Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China.

Abstract

CCCTC-binding factor (CTCF) is a transcription regulator with a complex role in gene regulation. The recognition and effects of CTCF on DNA sequences, chromosome barriers, and enhancer blocking are not well understood. Existing computational tools struggle to assess the regulatory potential of CTCF-binding sites and their impact on chromatin loop formation. Here we have developed a deep-learning model, DeepAnchor, to accurately characterize CTCF binding using high-resolution genomic/epigenomic features. This has revealed distinct chromatin and sequence patterns for CTCF-mediated insulation and looping. An optimized implementation of a previous loop model based on DeepAnchor score excels in predicting CTCF-anchored loops. We have established a compendium of CTCF-anchored loops across 52 human tissue/cell types, and this suggests that genomic disruption of these loops could be a general mechanism of disease pathogenesis. These computational models and resources can help investigate how CTCF-mediated cis-regulatory elements shape context-specific gene regulation in cell development and disease progression.

Keywords: 3D genome; CTCF; CTCF-mediated loop; cis-regulatory element; deep neural networks.