论文标题

量化测定:在癌细胞中评估的癌症治疗剂变异性的建模故事

Quantifying assays: A Modeling tale of variability in cancer therapeutics assessed on cancer cells

论文作者

Anguelov, Roumen, Manjunath, G, Phiri, Avulundiah E, Nyakudya, Trevor T, Bipath, Priyesh, Serem, June C, Hlophe, Yvette N

论文摘要

抑制信号通路涉及控制癌细胞活力,细胞分裂和死亡的细胞过程。创建的分析方案是为了查看所测试的药物的分子结构是否具有所需的抑制质量,通常在整个实验之间显示出很大的可变性,并且必须降低这种可变性的效果,同时提出推论。在本文中,我们通过描述抑制机制和激活抑制动力学的数学模型的镜头进行了实验数据的研究。通过从研​​究黑色素瘤细胞的CXCL12/CXCR4激活轴的抑制研究获得的测定数据来举例说明该方法。为了减轻数据的变异性对细胞活力测量的影响,理论上,细胞活力是根据时间的函数构建的,具体取决于几个参数。这些参数的值是通过使用实验数据来估计的。在理论上预先确定的形式中得出细胞活力的近似值,其优点是(i)对数据可变性的敏感性较小(ii)参数的估计值在生物学过程中直接解释,(iii)通过近似值来验证模型的质量(IV),该过程逐渐逐步验证了一个模型的估计量,该过程逐步验证了一个模型的过程。这些优势在概述方法的逐步实施中得到了证明。

Inhibiting a signalling pathway concerns controlling the cellular processes of a cancer cell's viability, cell division, and death. Assay protocols created to see if the molecular structures of the drugs being tested have the desired inhibition qualities often show great variability across experiments, and it is imperative to diminish the effects of such variability while inferences are drawn. In this paper we propose the study of experimental data through the lenses of a mathematical model depicting the inhibition mechanism and the activation-inhibition dynamics. The method is exemplified through assay data obtained from the study of inhibition of the CXCL12/CXCR4 activation axis for the melanoma cells. To mitigate the effects of the variability of the data on the cell viability measurement, the cell viability is theoretically constructed as a function of time depending on several parameters. The values of these parameters are estimated by using the experimental data. Deriving approximation for the cell viability in a theoretically pre-determined form has the advantages of (i) being less sensitive to data variability (ii) the estimated values of the parameters are interpreted directly in the biological processes, (iii) the amount of variability explained via the approximation validates the quality of the model, (iv) with the data integrated into the model one can derive a more complete view over the whole process. These advantages are demonstrated in the step-by-step implementation of the outlined approach.

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