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一种具有动态标记化功能的新型深度学习框架,用于识别染色质相互作用并进行基序重要性研究。

A novel deep learning framework with dynamic tokenization for identifying chromatin interactions along with motif importance investigation.

作者信息

Li Liangcan, Li Xin, Wu Hao

机构信息

School of Software, Shandong University, No. 1500, Shunshun Street, High tech Zone, Jinan, Shandong 250100, China.

Shenzhen Research Institute of Shandong University, Shenzhen 518063, Guangdong, China.

出版信息

Brief Bioinform. 2025 May 1;26(3). doi: 10.1093/bib/bbaf289.

Abstract

A comprehensive understanding of chromatin interaction networks is crucial for unraveling the regulatory mechanisms of gene expression. While various computational methods have been developed to predict chromatin interactions and address the limitations and high costs of high-throughput experimental techniques, their performance is often overestimated due to the specificity of chromatin interaction data. In this study, we proposed Inter-Chrom, a novel deep learning model integrating dynamic tokenization, DNABERT's word embedding, and the efficient channel attention mechanism to identify chromatin interactions using sequence and genomic features, leveraging a newly curated dataset. Experimental results demonstrate that Inter-Chrom outperforms existing methods on three cell line datasets. Additionally, we proposed a novel method for calculating motif importance and analyzed the motifs with high importance scores identified through this method, including those that have been extensively studied and others that have received limited attention to date. Inter-Chrom's robustness for input variations and superior ability to leverage sequence features position it as a powerful tool for advancing chromatin interaction research. The source code of Inter-Chrom is freely available at https://github.com/HaoWuLab-Bioinformatics/Inter-Chrom.

摘要

全面了解染色质相互作用网络对于揭示基因表达的调控机制至关重要。虽然已经开发了各种计算方法来预测染色质相互作用并解决高通量实验技术的局限性和高成本问题,但由于染色质相互作用数据的特异性,它们的性能往往被高估。在本研究中,我们提出了Inter-Chrom,这是一种新颖的深度学习模型,它整合了动态标记化、DNABERT的词嵌入和高效通道注意力机制,以利用新整理的数据集,通过序列和基因组特征识别染色质相互作用。实验结果表明,Inter-Chrom在三个细胞系数据集上优于现有方法。此外,我们提出了一种计算基序重要性的新方法,并分析了通过该方法确定的具有高重要性得分的基序,包括那些已经被广泛研究的基序和迄今受到有限关注的其他基序。Inter-Chrom对输入变化的稳健性以及利用序列特征的卓越能力使其成为推进染色质相互作用研究的有力工具。Inter-Chrom的源代码可在https://github.com/HaoWuLab-Bioinformatics/Inter-Chrom上免费获取。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a981/12204613/0989e5615185/bbaf289f1.jpg

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