Computer Science and Engineering, CEG Campus, Anna University, Chennai, Tamil Nadu, India.
Computer Science and Engineering, CEG Campus, Anna University, Chennai, Tamil Nadu, India.
Comput Biol Med. 2024 Nov;182:109145. doi: 10.1016/j.compbiomed.2024.109145. Epub 2024 Sep 20.
The greatest risk factor for many non-communicable diseases is aging. Studies on model organisms have demonstrated that genetic and chemical perturbation alterations can lengthen longevity and overall health. However, finding longevity-enhancing medications and their related targets is difficult.
In this work, we designed a novel drug repurposing model by identifying the interaction between aging-related genes or targets and drugs similar to aging disease. Each disease is associated with certain specific genetic factors for the occurrence of that disease. The factors include gene expression, pathway, miRNA, and degree of genes in the protein-protein interaction network. In this paper, we aim to find the drugs that prolong the life span of humans with their aging-related targets using the above-mentioned factors. In addition, the contribution or importance of each factor may vary among drugs and targets. Therefore, we designed a novel multi-layer random walk-based network representation learning model including node and edge weight to learn the features of drugs and targets respectively.
The performance of the proposed model is demonstrated using k-fold cross-validation (k = 5). This model achieved better performance with scores of 0.93 and 0.91 for precision and recall respectively. The drugs identified by the system are evaluated to be potential candidates for aging since the degree of interaction between the potential drugs and their gene sets are high. In addition, the genes that are interacting with drugs produce the same biological functions. Hence the life span of the human will be increased or prolonged.
许多非传染性疾病的最大风险因素是衰老。对模式生物的研究表明,遗传和化学扰动改变可以延长寿命和整体健康。然而,寻找延长寿命的药物及其相关靶点是困难的。
在这项工作中,我们通过鉴定与衰老相关的基因或靶标与类似衰老疾病的药物之间的相互作用,设计了一种新的药物再利用模型。每种疾病都与该疾病发生的某些特定遗传因素有关。这些因素包括基因表达、途径、miRNA 和蛋白质-蛋白质相互作用网络中基因的程度。在本文中,我们旨在使用上述因素,找到与人类衰老相关的靶点延长寿命的药物。此外,药物和靶点之间的每个因素的贡献或重要性可能有所不同。因此,我们设计了一种新的基于多层随机游走的网络表示学习模型,包括节点和边权重,分别学习药物和靶点的特征。
通过 k 折交叉验证(k=5)演示了所提出模型的性能。该模型的精度和召回率得分分别为 0.93 和 0.91,性能更好。系统识别的药物被评估为衰老的潜在候选药物,因为潜在药物与其基因集之间的相互作用程度较高。此外,与药物相互作用的基因产生相同的生物学功能。因此,人类的寿命将会增加或延长。