Spadaro Austin, Sharma Alok, Dehzangi Iman
Center for Computational and Integrative Biology, Rutgers University, Camden, NJ, USA.
Institute for Integrated and Intelligent Systems, Griffith University, Brisbane, Australia.
Methods Mol Biol. 2025;2941:177-187. doi: 10.1007/978-1-0716-4623-6_11.
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.
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。