论文标题

使用基于事件的分层种群的模型来分析APOE对阿尔茨海默氏病进展的影响

Analyzing the effect of APOE on Alzheimer's disease progression using an event-based model for stratified populations

论文作者

Venkatraghavan, Vikram, Klein, Stefan, Fani, Lana, Ham, Leontine S., Vrooman, Henri, Ikram, M. Kamran, Niessen, Wiro J., Bron, Esther E.

论文摘要

阿尔茨海默氏病(AD)是痴呆症的最常见形式,在表型上是异质的。 APOE是一个试验基因,与AD中的表型异质性相关。在这项工作中,我们使用基于歧视事件的模型(DEBM)确定了APOE等位基因对AD疾病进展时间表的影响。由于DEBM是一个数据驱动的模型,因此与将模型拟合在整个数据集中相比,分为较小的疾病亚组将导致更多不准确的模型。因此,我们的次要目的是提出和评估新方法,在这些方法中,我们将DEBM的不同步骤分为群体特定和特定组的零件,在该部分中,整个数据集用于训练群体中的零件,并且只有来自特定组的数据仅用于训练DEBM的小组特异性部分。我们进行了仿真实验,以基准提出的方法的准确性并选择最佳方法。随后,选择的方法应用于417个认知正常,235个轻度认知受损的基线数据,他们在3年内转化为AD,而来自阿尔茨海默氏病神经影像学计划(ADNI)数据集中的342名AD患者,以使APOERIELIOL对疾病进度的效果效果AD AD AD AD AD AD的效果。提出的模型可以有助于理解该疾病,并在选择一组均匀的症状受试者群体中,以临床试验的症状出现。

Alzheimer's disease (AD) is the most common form of dementia and is phenotypically heterogeneous. APOE is a triallelic gene which correlates with phenotypic heterogeneity in AD. In this work, we determined the effect of APOE alleles on the disease progression timeline of AD using a discriminative event-based model (DEBM). Since DEBM is a data-driven model, stratification into smaller disease subgroups would lead to more inaccurate models as compared to fitting the model on the entire dataset. Hence our secondary aim is to propose and evaluate novel approaches in which we split the different steps of DEBM into group-aspecific and group-specific parts, where the entire dataset is used to train the group-aspecific parts and only the data from a specific group is used to train the group-specific parts of the DEBM. We performed simulation experiments to benchmark the accuracy of the proposed approaches and to select the optimal approach. Subsequently, the chosen approach was applied to the baseline data of 417 cognitively normal, 235 mild cognitively impaired who convert to AD within 3 years, and 342 AD patients from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset to gain new insights into the effect of APOE carriership on the disease progression timeline of AD. The presented models could aid understanding of the disease, and in selecting homogeneous group of presymptomatic subjects at-risk of developing symptoms for clinical trials.

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