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CNN-Meth:一种利用基于进化信息的蛋白质建模准确预测赖氨酸甲基化位点的工具。

CNN-Meth: A Tool to Accurately Predict Lysine Methylation Sites Using Evolutionary Information-Based Protein Modeling.

作者信息

Spadaro Austin, Sharma Alok, Dehzangi Iman

机构信息

Center for Computational and Integrative Biology, Rutgers University, Camden, NJ, USA.

Institute for Integrated and Intelligent Systems, Griffith University, Brisbane, Australia.

出版信息

Methods Mol Biol. 2025;2941:177-187. doi: 10.1007/978-1-0716-4623-6_11.

DOI:10.1007/978-1-0716-4623-6_11
PMID:40601258
Abstract

Lysine methylation is a crucial posttranslational modification influencing both histone and nonhistone protein functions. Disruptions in lysine methyltransferase activity are linked to numerous diseases, including various cancers and developmental disorders. Accurate identification of lysine methylation sites is essential for early diagnosis and therapeutic development. Here, we present CNN-Meth, a newly developed Web-based utility that employs a convolutional neural network (CNN) to predict lysine methylation sites. CNN-Meth leverages evolutionary, structural, and physicochemical data alongside binary encoding for its training process. Evolutionary and structural features used to build CNN-Meth are extracted using protein modeling, which works similarly to using Protein Language Models (PLM). Unlike traditional approaches that rely on manually extracted features, CNN-Meth uses CNNs for automated feature extraction, ensuring minimal information loss. This novel methodology enhances prediction accuracy, achieving 96.0% Accuracy, 85.1% Sensitivity, 96.4% Specificity, and a Matthew's Correlation Coefficient (MCC) of 0.65. This demonstrates the possible effectiveness of using PLM to predict Methylation sites as a future direction. The CNN-Meth tool and its source code are readily accessible at https://github.com/MLBC-lab/CNN-Meth , providing a robust resource for researchers and clinicians.

摘要

赖氨酸甲基化是一种关键的翻译后修饰,影响组蛋白和非组蛋白的功能。赖氨酸甲基转移酶活性的破坏与多种疾病相关,包括各种癌症和发育障碍。准确识别赖氨酸甲基化位点对于早期诊断和治疗开发至关重要。在此,我们展示了CNN-Meth,这是一种新开发的基于网络的工具,它采用卷积神经网络(CNN)来预测赖氨酸甲基化位点。CNN-Meth在其训练过程中利用进化、结构和物理化学数据以及二进制编码。用于构建CNN-Meth的进化和结构特征是通过蛋白质建模提取的,其工作方式类似于使用蛋白质语言模型(PLM)。与依赖手动提取特征的传统方法不同,CNN-Meth使用CNN进行自动特征提取,确保信息损失最小。这种新颖的方法提高了预测准确性,准确率达到96.0%,灵敏度达到85.1%,特异性达到96.4%,马修斯相关系数(MCC)为0.65。这证明了使用PLM预测甲基化位点作为未来方向的潜在有效性。CNN-Meth工具及其源代码可在https://github.com/MLBC-lab/CNN-Meth上轻松获取,为研究人员和临床医生提供了强大的资源。

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本文引用的文献

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TransPTM: a transformer-based model for non-histone acetylation site prediction.TransPTM:一种基于转换器的非组蛋白乙酰化位点预测模型。
Brief Bioinform. 2024 Mar 27;25(3). doi: 10.1093/bib/bbae219.
2
Predicting lysine methylation sites using a convolutional neural network.使用卷积神经网络预测赖氨酸甲基化位点。
Methods. 2024 Jun;226:127-132. doi: 10.1016/j.ymeth.2024.04.007. Epub 2024 Apr 9.
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PepCNN deep learning tool for predicting peptide binding residues in proteins using sequence, structural, and language model features.
PepCNN 深度学习工具,用于使用序列、结构和语言模型特征预测蛋白质中的肽结合残基。
Sci Rep. 2023 Nov 28;13(1):20882. doi: 10.1038/s41598-023-47624-5.
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CNN-Pred: Prediction of single-stranded and double-stranded DNA-binding protein using convolutional neural networks.CNN-Pred:使用卷积神经网络预测单链和双链 DNA 结合蛋白。
Gene. 2023 Feb 15;853:147045. doi: 10.1016/j.gene.2022.147045. Epub 2022 Nov 26.
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Improving protein succinylation sites prediction using embeddings from protein language model.利用蛋白质语言模型的嵌入来改进蛋白质琥珀酰化位点预测。
Sci Rep. 2022 Oct 8;12(1):16933. doi: 10.1038/s41598-022-21366-2.
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Interpretable machine learning identification of arginine methylation sites.可解释机器学习鉴定精氨酸甲基化位点。
Comput Biol Med. 2022 Aug;147:105767. doi: 10.1016/j.compbiomed.2022.105767. Epub 2022 Jun 21.
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CPLM 4.0: an updated database with rich annotations for protein lysine modifications.CPLM 4.0:一个具有丰富赖氨酸修饰注释信息的更新数据库。
Nucleic Acids Res. 2022 Jan 7;50(D1):D451-D459. doi: 10.1093/nar/gkab849.
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Proteomic landscape of Alzheimer's Disease: novel insights into pathogenesis and biomarker discovery.阿尔茨海默病的蛋白质组学全景:发病机制和生物标志物发现的新见解。
Mol Neurodegener. 2021 Aug 12;16(1):55. doi: 10.1186/s13024-021-00474-z.
9
Posttranslational modifications in proteins: resources, tools and prediction methods.蛋白质的翻译后修饰:资源、工具和预测方法。
Database (Oxford). 2021 Apr 7;2021. doi: 10.1093/database/baab012.
10
Epigenetics and beyond: targeting writers of protein lysine methylation to treat disease.表观遗传学及其他:以蛋白质赖氨酸甲基化写作者为靶点治疗疾病。
Nat Rev Drug Discov. 2021 Apr;20(4):265-286. doi: 10.1038/s41573-020-00108-x. Epub 2021 Jan 19.