Kumar Rupesh, Haider Shazia
Department of Biotechnology, Jaypee Institute of Information Technology, Noida, Sec-62, Uttar Pradesh, India.
IBRO Neurosci Rep. 2021 Dec 7;12:25-44. doi: 10.1016/j.ibneur.2021.12.002. eCollection 2022 Jun.
Amyotrophic Lateral Sclerosis (ALS) is a fatal disease, progressive nature characterizes by loss of both upper and lower motor neuron functions. One of the major challenge is to understand the mechanism of ALS multifactorial nature. We aimed to explore some key genes related to ALS through bioinformatics methods for its therapeutic intervention. Here, we applied a systems biology approach involving experimentally validated 148 ALS-associated proteins and construct ALS protein-protein interaction network (ALS-PPIN). The network was further statistically analysed and identified bottleneck-hubs. The network is also subjected to identify modules which could have similar functions. The interaction between the modules and bottleneck-hubs provides the functional regulatory role of the ALS mechanism. The ALS-PPIN demonstrated a hierarchical scale-free nature. We identified 17 bottleneck-hubs, in which , and were the high degree nodes (hubs) in ALS-PPIN. was found to control highly cluster modules and play a vital role in the stability of the overall network followed by , and . as a common connector for and bottleneck-hubs. The functional and disease association analysis showed ALS has a strong correlation with mRNA processing, protein deubiquitination, and neoplasms, nervous system, immune system disease classes. In the future, biochemical investigation of the observed bottleneck-hubs and their interacting partners could provide a further understanding of their role in the pathophysiology of ALS.
肌萎缩侧索硬化症（ALS）是一种致命疾病，其进展性特征为上下运动神经元功能丧失。主要挑战之一是了解ALS多因素性质的机制。我们旨在通过生物信息学方法探索一些与ALS相关的关键基因，以进行治疗干预。在此，我们应用了一种系统生物学方法，涉及148种经实验验证的与ALS相关的蛋白质，并构建了ALS蛋白质-蛋白质相互作用网络（ALS-PPIN）。对该网络进行了进一步的统计分析并确定了瓶颈枢纽。该网络还用于识别可能具有相似功能的模块。模块与瓶颈枢纽之间的相互作用提供了ALS机制的功能调节作用。ALS-PPIN呈现出分层的无标度性质。我们确定了17个瓶颈枢纽，其中， 、 和 是ALS-PPIN中的高度节点（枢纽）。发现 控制高度聚集的模块，并在整个网络的稳定性中发挥至关重要的作用，其次是 、 和 。 作为 和 瓶颈枢纽的共同连接点。功能和疾病关联分析表明，ALS与mRNA加工、蛋白质去泛素化以及肿瘤、神经系统、免疫系统疾病类别密切相关。未来，对观察到的瓶颈枢纽及其相互作用伙伴进行生化研究，可能会进一步了解它们在ALS病理生理学中的作用。
