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使用非线性混合效应框架对患者来源和细胞系来源异种移植进行经典肿瘤生长模型比较。

Comparison of classical tumour growth models for patient derived and cell-line derived xenografts using the nonlinear mixed-effects framework.

机构信息

DMPK Oncology R&D, AstraZeneca, Cambridge, UK.

Early Computational Oncology, Research and Early Development, Oncology R&D, AstraZeneca, Cambridge, UK.

出版信息

J Biol Dyn. 2022 Dec;16(1):160-185. doi: 10.1080/17513758.2022.2061615.

Abstract

In this study we compare seven mathematical models of tumour growth using nonlinear mixed-effects which allows for a simultaneous fitting of multiple data and an estimation of both mean behaviour and variability. This is performed for two large datasets, a patient-derived xenograft (PDX) dataset consisting of 220 PDXs spanning six different tumour types and a cell-line derived xenograft (CDX) dataset consisting of 25 cell lines spanning eight tumour types. Comparison of the models is performed by means of visual predictive checks (VPCs) as well as the Akaike Information Criterion (AIC). Additionally, we fit the models to 500 bootstrap samples drawn from the datasets to expand the comparison of the models under dataset perturbations and understand the growth kinetics that are best fitted by each model. Through qualitative and quantitative metrics the best models are identified the effectiveness and practicality of simpler models is highlighted.

摘要

在本研究中,我们使用非线性混合效应比较了七种肿瘤生长的数学模型,该模型允许同时拟合多个数据,并估计均值行为和变异性。这是针对两个大型数据集进行的,一个是包含 220 个 PDX 的患者来源异种移植 (PDX) 数据集,涵盖六种不同的肿瘤类型,另一个是包含 25 个细胞系的异种移植 (CDX) 数据集,涵盖八种肿瘤类型。通过可视化预测检查 (VPC) 以及赤池信息量准则 (AIC) 对模型进行比较。此外,我们还对从数据集中抽取的 500 个 bootstrap 样本进行拟合,以扩展在数据集扰动下对模型的比较,并了解每个模型最适合的生长动力学。通过定性和定量指标,确定了最佳模型,突出了更简单模型的有效性和实用性。

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