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Global Sensitivity Analysis for a Model of B-Cell Chronic Lymphocytic Leukemia Disease Trajectories

机译:B细胞慢性淋巴细胞白血病术术模型的全局敏感性分析

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This paper implements global sensitivity analysis in the Savvopoulos et al. (2014) mathematical model of B cell chronic lymphocytic leukemia (B-CLL); this dynamic model represents a framework for modelling dynamic B-CLL trajectories. B-CLL is a heterogeneous, slowly-progressing disease where a type of white blood cell, B lymphocytes, accumulates in bone marrow, peripheral blood, lymph nodes and spleen. The Savvopoulos et al. (2014) modelling framework integrates both temporal and spatial disease aspects; delay differential equations capture latency in the cell proliferation cycle and population balance equations between disease centres represent inter-tissue B-CLL migration. This manuscript conducts global sensitivity analysis using the random sampling - high dimensional mathematical representation (RS-HDMR) method to: (1) uncover which are the most critical model parameters; (2) analyse the system of model equations; (3) provide clinically-relevant patient testing recommendations leading to effective model parametrisations.
机译:本文在Savvopoulos等人中实现了全局敏感性分析。 (2014)B细胞慢性淋巴细胞白血病的数学模型(B-CLL);该动态模型代表了一种用于建模动态B-CLL轨迹的框架。 B-CLL是一种异质,缓慢进展的疾病,其中一种白细胞,B淋巴细胞,累积在骨髓,外周血,淋巴结和脾脏中。 Savvopoulos等人。 (2014)建模框架整合了时间和空间疾病方面;延迟微分方程捕获细胞增殖周期中的潜伏期和疾病中心之间的群体平衡方程代表组织间B-CLL迁移。该稿件使用随机采样 - 高维数学表示(RS-HDMR)方法来进行全局敏感性分析:(1)揭示是最关键的模型参数; (2)分析模型方程的系统; (3)提供临床相关的患者测试建议,导致有效的模型参数化。

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