Elghaish Reem A, Attallah Nayera E, Khaled Hesham, Mekawy Asmaa S, Elserafy Menattallah, Badr Eman
University of Science and Technology, Zewail City of Science and Technology, Giza, 12578, Egypt.
Center for Genomics, Helmy Institute for Medical Sciences, Zewail City of Science and Technology, Giza, 12578, Egypt.
Sci Rep. 2025 Apr 26;15(1):14590. doi: 10.1038/s41598-025-97363-y.
The cytoskeleton comprises polymers from protein filaments shaped in an organized structure. This structure contributes significantly to the cell's function and viability. Decades of research have implicated that the cytoskeleton's dynamic nature is associated with downstream signaling events that further regulate cellular activity and control aging and neurodegeneration. This study aims to investigate the transcriptional changes of the cytoskeletal genes and their regulators in five age-related diseases: Hypertrophic Cardiomyopathy (HCM), Coronary Artery Disease (CAD), Alzheimer's disease (AD), Idiopathic Dilated Cardiomyopathy (IDCM), and Type 2 Diabetes Mellitus (T2DM). An integrative approach of machine learning-based models and differential expression analysis was employed to identify potential biomarkers based on the cytoskeletal genes. Multiple machine-learning algorithms were used, where the Support Vector machines (SVM) classifier achieved the highest accuracy. The study highlighted 17 genes involved in the cytoskeleton's structure and regulation associated with age-related diseases. The results provide a holistic overview of the role of transcriptionally dysregulated cytoskeletal genes in age-related diseases. This study pinpoints cytoskeletal genes and regulators of the cytoskeleton that can be utilized as potential markers and drug targets.
细胞骨架由具有有序结构的蛋白质丝聚合物组成。这种结构对细胞的功能和生存能力有显著贡献。数十年的研究表明,细胞骨架的动态性质与下游信号事件相关,这些信号事件进一步调节细胞活动并控制衰老和神经退行性变。本研究旨在调查细胞骨架基因及其调控因子在五种与年龄相关疾病中的转录变化:肥厚型心肌病(HCM)、冠状动脉疾病(CAD)、阿尔茨海默病(AD)、特发性扩张型心肌病(IDCM)和2型糖尿病(T2DM)。采用基于机器学习的模型和差异表达分析的综合方法,基于细胞骨架基因识别潜在的生物标志物。使用了多种机器学习算法,其中支持向量机(SVM)分类器达到了最高准确率。该研究突出了17个与细胞骨架结构和调控相关且与年龄相关疾病有关的基因。结果提供了转录失调的细胞骨架基因在年龄相关疾病中作用的整体概述。本研究确定了可作为潜在标志物和药物靶点的细胞骨架基因及其调控因子。