DataSheet2_Mathematical modeling and application of IL-1β/TNF signaling pathway in regulating chondrocyte apoptosis.zip

Introduction: Mathematical model can be used to model complex biological processes, and have shown potential in describing apoptosis in chondrocytes.
Method: In order to investigate the regulatory mechanisms of TNF signaling pathway in regulating chondrocyte apoptosis, a fractional-order differential equation model is proposed to describe the dynamic behavior and mutual interaction of apoptosis-related genes under the activation of TNF signaling pathway. Compared with the traditional molecular biology techniques, the proposed mathematical modeling has advantages to providing a more comprehensive understanding of the regulatory mechanisms of TNF signaling pathway in chondrocyte apoptosis.
Result: In this paper, differentially expressed genes induced by IL-1β in human chondrocyte apoptosis are screened using high-throughput sequencing. It is found that they were significantly enriched in the TNF signaling pathway. Therefore, a mathematical model of the TNF signaling pathway is built. Using real-time PCR experiments, mRNA data is measured and used to identify the model parameters, as well as the correlation coefficient. Finally, the sensitivity of the model parameters is discussed by using numerical simulation methods, which can be used to predict the effects of different interventions and explore the optimal intervention strategies for regulating chondrocyte apoptosis.
Discussion: Therefore, fractional-order differential equation modeling plays an important role in understanding the regulatory mechanisms of TNF signaling pathway in chondrocyte apoptosis and its potential clinical applications.

引言：数学模型可用于刻画复杂的生物过程，且在描述软骨细胞（chondrocytes）凋亡方面已展现出应用潜力。方法：为探究肿瘤坏死因子（TNF）信号通路调控软骨细胞凋亡的分子机制，本研究提出一种分数阶微分方程（fractional-order differential equation）模型，用以刻画TNF信号通路激活状态下凋亡相关基因的动态行为与相互作用关系。相较于传统分子生物学实验技术，本研究所提出的数学建模方法能够更全面地阐释TNF信号通路在软骨细胞凋亡调控中的作用机制。结果：本研究通过高通量测序（high-throughput sequencing）技术，筛选出白细胞介素1β（IL-1β）诱导的人软骨细胞凋亡相关差异表达基因。富集分析结果显示，这些基因显著富集于TNF信号通路。据此，本研究构建了TNF信号通路的数学模型。通过实时荧光定量PCR（real-time PCR）实验获取信使RNA（mRNA）表达数据，用以辨识模型参数与相关系数。最后，本研究采用数值模拟方法探讨了模型参数的敏感性，该分析可用于预测不同干预手段的效果，并探索调控软骨细胞凋亡的最优干预策略。讨论：综上，分数阶微分方程建模在阐释TNF信号通路调控软骨细胞凋亡的分子机制及其潜在临床应用方面具有重要价值。