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iEnhancer-GDM:一种基于生成对抗网络和多头注意力机制的深度学习框架,用于识别增强子及其强度。

iEnhancer-GDM: A Deep Learning Framework Based on Generative Adversarial Network and Multi-head Attention Mechanism to Identify Enhancers and Their Strength.

作者信息

Yang Xiaomei, Liao Meng, Ye Bin, Xia Junfeng, Zhao Jianping

机构信息

College of Mathematics and System Sciences, Xinjiang University, Urumqi, 830017, China.

Institutes of Physical Science and Information Technology, Anhui University, Hefei, 230601, China.

出版信息

Interdiscip Sci. 2025 May 7. doi: 10.1007/s12539-025-00703-9.

DOI:10.1007/s12539-025-00703-9
PMID:40335860
Abstract

Enhancers are short DNA fragments capable of significantly increase the frequency of gene transcription. They often exert their effects on targeted genes over long distances, either in cis or in trans configurations. Identifying enhancers poses a challenge due to their variable position and sensitivities. Genetic variants within enhancer regions have been implicated in human diseases, highlighting critical importance of enhancers identification and strength prediction. Here, we develop a two-layer predictor named iEnhancer-GDM to identify enhancers and to predict enhancer strength. To address the challenges posed by the limited size of enhancer training dataset, which could cause issues such as model overfitting and low classification accuracy, we introduce a Wasserstein generative adversarial network (WGAN-GP) to augment the dataset. We employ a dna2vec embedding layer to encode raw DNA sequences into numerical feature representations, and then integrate multi-scale convolutional neural network, bidirectional long short-term memory network and multi-head attention mechanism for feature representation and classification. Our results validate the effectiveness of data augmentation in WGAN-GP. Our model iEnhancer-GDM achieves superior performance on an independent test dataset, and outperforms the existing models with improvements of 2.45% for enhancer identification and 11.5% for enhancer strength prediction by benchmarking against current methods. iEnhancer-GDM advances the precise enhancer identification and strength prediction, thereby helping to understand the functions of enhancers and their associations on genomics.

摘要

增强子是能够显著提高基因转录频率的短DNA片段。它们通常以顺式或反式构型在远距离对靶基因发挥作用。由于增强子的位置和敏感性各不相同,识别增强子具有挑战性。增强子区域内的基因变异与人类疾病有关,这突出了增强子识别和强度预测的至关重要性。在此,我们开发了一种名为iEnhancer-GDM的两层预测器,用于识别增强子并预测增强子强度。为了解决增强子训练数据集规模有限所带来的挑战,这些挑战可能导致模型过拟合和分类准确率低等问题,我们引入了瓦瑟斯坦生成对抗网络(WGAN-GP)来扩充数据集。我们采用dna2vec嵌入层将原始DNA序列编码为数值特征表示,然后整合多尺度卷积神经网络、双向长短期记忆网络和多头注意力机制进行特征表示和分类。我们的结果验证了WGAN-GP中数据增强的有效性。我们的模型iEnhancer-GDM在独立测试数据集上取得了优异的性能,通过与当前方法进行基准测试,在增强子识别方面比现有模型提高了2.45%,在增强子强度预测方面提高了11.5%。iEnhancer-GDM推进了精确的增强子识别和强度预测,从而有助于理解增强子的功能及其在基因组学上的关联。

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本文引用的文献

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Active enhancers: recent research advances and insights into disease.活性增强子:疾病研究的最新进展和见解。
Biol Direct. 2024 Nov 12;19(1):112. doi: 10.1186/s13062-024-00559-x.
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Fundamentals for predicting transcriptional regulations from DNA sequence patterns.从 DNA 序列模式预测转录调控的基础。
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Enhancer selectivity in space and time: from enhancer-promoter interactions to promoter activation.增强子在时空上的选择性:从增强子-启动子相互作用到启动子激活。
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Enhancer dynamics: Unraveling the mechanism of transcriptional bursting.增强子动态:解析转录爆发的机制。
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Multimodal single cell analysis infers widespread enhancer co-activity in a lymphoblastoid cell line.多模态单细胞分析推断淋巴母细胞系中广泛的增强子共活性。
Commun Biol. 2023 May 26;6(1):563. doi: 10.1038/s42003-023-04954-4.
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Sequence determinants of human gene regulatory elements.人类基因调控元件的序列决定因素。
Nat Genet. 2022 Mar;54(3):283-294. doi: 10.1038/s41588-021-01009-4. Epub 2022 Feb 21.
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A comparison of experimental assays and analytical methods for genome-wide identification of active enhancers.用于全基因组鉴定活性增强子的实验分析与分析方法的比较。
Nat Biotechnol. 2022 Jul;40(7):1056-1065. doi: 10.1038/s41587-022-01211-7. Epub 2022 Feb 17.
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ReMap 2022: a database of Human, Mouse, Drosophila and Arabidopsis regulatory regions from an integrative analysis of DNA-binding sequencing experiments.ReMap 2022:一个整合了 DNA 结合测序实验分析的人类、小鼠、果蝇和拟南芥调控区域数据库。
Nucleic Acids Res. 2022 Jan 7;50(D1):D316-D325. doi: 10.1093/nar/gkab996.
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Anal Biochem. 2021 Oct 1;630:114318. doi: 10.1016/j.ab.2021.114318. Epub 2021 Aug 5.
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iEnhancer-EBLSTM: Identifying Enhancers and Strengths by Ensembles of Bidirectional Long Short-Term Memory.iEnhancer-EBLSTM:通过双向长短期记忆集成识别增强子及其强度
Front Genet. 2021 Mar 23;12:665498. doi: 10.3389/fgene.2021.665498. eCollection 2021.