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CREaTor: zero-shot cis-regulatory pattern modeling with attention mechanisms.

Yongge Li^1,2, Fusong Ju¹, Zhiyuan Chen^1,3

¹Microsoft Research AI4Science, Beijing, China.

|November 24, 2023

Summary

We developed CREaTor, a deep learning tool to link gene regulatory elements to target genes. It accurately predicts gene expression in new cell types using only RNA-seq and ChIP-seq data.

Keywords:

Cis-regulatory pattern Enhancer-gene interaction Epigenetics Gene expression Gene regulation

Related Experiment Videos

Area of Science:

Genomics
Computational Biology
Molecular Biology

Background:

Linking cis-regulatory sequences to their target genes is crucial for understanding gene regulation but remains a significant challenge.
Existing methods often require prior knowledge of specific interactions or extensive training data for each cell type.

Purpose of the Study:

To introduce CREaTor, an attention-based deep neural network for modeling cis-regulatory patterns.
To enable cell type-specific cis-regulatory pattern modeling without prior interaction knowledge or retraining.

Main Methods:

Developed CREaTor, a deep neural network utilizing attention mechanisms to model cis-regulatory patterns.
Implemented a training strategy predicting gene expression from candidate cis-regulatory elements (cCREs).
Leveraged RNA-sequencing (RNA-seq) and ChIP-sequencing (ChIP-seq) data for model training and application.

Main Results:

CREaTor effectively models cis-regulatory patterns for genomic elements up to 2 megabases (Mb) from target genes.
The model demonstrates "zero-shot" capability, predicting cell type-specific patterns in new cell types without specific training.
Achieved generalization across diverse cell types using only RNA-seq and ChIP-seq data.

Conclusions:

CREaTor offers a powerful and generalizable approach to link cis-regulatory sequences to target genes.
The zero-shot learning capability significantly reduces the need for cell-type-specific training data.
This method facilitates a deeper understanding of gene regulation across various cellular contexts.