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Updated: Jun 10, 2025
Dissection of Enhancer Function Using Multiplex CRISPR-based Enhancer Interference in Cell Lines
Published on: June 2, 2018
A novel interpretable deep learning-based computational framework designed synthetic enhancers with broad
Zhaohong Li1,2, Yuanyuan Zhang1,2, Bo Peng3,4
1Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Key Laboratory of Livestock and Poultry Multi-Omics of MARA, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Buxin Road NO. 97, Dapeng District, Shenzhen 518124, China.
We developed DREAM, a deep learning tool for designing synthetic enhancers with predictable activity. Our engineered enhancers are highly potent and function across diverse species, advancing gene regulation applications.
Area of Science:
- Genomics
- Molecular Biology
- Bioengineering
Background:
- Enhancers are crucial for gene expression and cell identity.
- Identifying sequence determinants of enhancer activity is challenging.
- Current methods lack precision in synthetic enhancer design.
Purpose of the Study:
- To introduce DREAM, a deep learning framework for designing synthetic enhancers.
- To predict enhancer activity based on DNA sequence.
- To engineer potent and versatile cis-regulatory elements.
Main Methods:
- Developed the DREAM (DNA cis-Regulatory Elements with controllable Activity design platforM) framework.
- Utilized deep learning to analyze enhancer screening data.
- Applied DREAM for sequence-based enhancer activity prediction and design.
Main Results:
- Engineered synthetic enhancers 3.6-fold more potent than the strongest Drosophila enhancer.
- Demonstrated conserved functionality of designed enhancers across species.
- Successfully designed silencers and cell line-specific enhancers using DREAM.
Conclusions:
- DREAM provides an interpretable approach for synthetic cis-regulatory element design.
- The framework learned conserved enhancer regulatory grammar.
- DREAM offers a versatile platform for gene therapy and biosynthetic engineering applications.
