Patient-specific models from inter-patient biological models and clinical records

E. Tronci, Toni Mancini, Ivano Salvo, S. Sinisi, F. Mari, I. Melatti, A. Massini, Francesco Davi, T. Dierkes, R. Ehrig, S. Röblitz, B. Leeners, T. Kruger, M. Egli, F. Ille
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引用次数: 38

Abstract

One of the main goals of systems biology models in a health-care context is to individualise models in order to compute patient-specific predictions for the time evolution of species (e.g., hormones) concentrations. In this paper we present a statistical model checking based approach that, given an inter-patient model and a few clinical measurements, computes a value for the model parameter vector (model individualisation) that, with high confidence, is a global minimum for the function evaluating the mismatch between the model predictions and the available measurements. We evaluate effectiveness of the proposed approach by presenting experimental results on using the GynCycle model (describing the feedback mechanisms regulating a number of reproductive hormones) to compute patient-specific predictions for the time evolution of blood concentrations of E2 (Estradiol), P4 (Progesterone), FSH (Follicle-Stimulating Hormone) and LH (Luteinizing Hormone) after a certain number of clinical measurements.
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患者特异性模型来自患者间生物学模型和临床记录
在卫生保健环境中,系统生物学模型的主要目标之一是使模型个性化,以便计算特定于患者的物种(例如激素)浓度的时间进化预测。在本文中,我们提出了一种基于统计模型检查的方法,该方法给定患者间模型和一些临床测量,计算模型参数向量(模型个性化)的值,该值具有高置信度,是评估模型预测与可用测量之间不匹配的函数的全局最小值。我们通过使用gyyncycle模型(描述调节多种生殖激素的反馈机制)计算特定患者在一定数量的临床测量后血液中E2(雌二醇)、P4(黄体酮)、FSH(促卵泡激素)和LH(黄体生成素)浓度的时间演变的实验结果来评估所提出方法的有效性。
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