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Inferring CTCF-binding patterns and anchored loops across human tissues and cell types
Hang Xu1,2, Xianfu Yi3, Xutong Fan3
1Department 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.
Patterns (New York, N.Y.)
|August 21, 2023
Summary
We developed DeepAnchor, a deep-learning model to characterize CTCF binding and predict CTCF-anchored loops. This tool reveals how CTCF-mediated loops impact gene regulation and disease pathogenesis.
Area of Science:
- Genomics
- Epigenetics
- Computational Biology
Background:
- CCCTC-binding factor (CTCF) is a key transcription regulator with poorly understood roles in DNA sequence recognition, chromosome barrier function, and enhancer blocking.
- Current computational tools are limited in assessing CTCF-binding sites' regulatory potential and their impact on chromatin loop formation.
Purpose of the Study:
- To develop a deep-learning model for accurate characterization of CTCF binding using high-resolution genomic and epigenomic features.
- To identify distinct chromatin and sequence patterns associated with CTCF-mediated insulation and looping.
- To establish a compendium of CTCF-anchored loops and investigate their role in disease.
Main Methods:
- Development of a deep-learning model, DeepAnchor, for CTCF binding characterization.
- Utilizing high-resolution genomic and epigenomic data as input features.
- Optimization of a loop prediction model using DeepAnchor scores.
- Creation of a compendium of CTCF-anchored loops across 52 human tissue/cell types.
Main Results:
- DeepAnchor accurately characterizes CTCF binding, revealing distinct sequence and chromatin patterns for insulation and looping.
- An optimized loop model based on DeepAnchor scores demonstrates high accuracy in predicting CTCF-anchored loops.
- A comprehensive compendium of CTCF-anchored loops across diverse human cell types was established.
Conclusions:
- DeepAnchor provides a powerful tool for understanding CTCF-mediated gene regulation.
- Genomic disruption of CTCF-anchored loops may represent a common mechanism in disease pathogenesis.
- The developed models and resources facilitate research into CTCF's role in cellular development and disease.
