Neural network on interval-censored data with application to the prediction of Alzheimer's disease.

Neural network on interval-censored data with application to the prediction of Alzheimer's disease.
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DOI:
10.1111/biom.13734
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发表时间:
2023-09
期刊:
影响因子:
1.9
通讯作者:
Ding, Ying
Ding, Ying
中科院分区:
数学3区
文献类型:
--
作者:
Sun, Tao;Ding, Ying

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阿尔茨海默病(AD)是一种进行性多基因疾病,每年影响数百万人。考虑到AD的有效治疗方法很少,因此非常需要开发一种准确的模型,以基于个体的遗传特征预测完整的疾病进展概况,用于早期预防和临床管理。这项工作使用了阿尔茨海默病神经成像倡议(ADNI)研究的所有四个阶段的数据,包括1740名具有800万个遗传变异的个体。我们解决了该数据中的几个挑战,其特征在于大规模遗传数据,间歇性评估导致的间隔删失结果以及一个研究阶段(ADNIGO)的左截断。具体来说,我们首先开发了一个半参数转换模型的区间删失和左截断数据和估计参数通过筛子的方法。然后,我们提出了一个计算效率的广义分数测试,以确定与AD进展相关的变异。接下来,我们在区间删失数据(NN-IC)上实现了一种新的神经网络,以使用从全基因组测试中识别出的顶级变异来构建预测模型。综合仿真研究表明,神经网络集成电路优于现有的几种方法的预测精度。最后,我们将NN-IC应用于完整的ADNI数据,并成功识别出具有不同进展风险特征的亚组。本文编写中使用的数据来自ADNI数据库。
Alzheimer’s disease (AD) is a progressive and polygenic disorder that affects millions of individuals each year. Given that there have been few effective treatments yet for AD, it is highly desirable to develop an accurate model to predict the full disease progression profile based on an individual’s genetic characteristics for early prevention and clinical management. This work uses data composed of all four phases of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) study, including 1740 individuals with 8 million genetic variants. We tackle several challenges in this data, characterized by large-scale genetic data, interval-censored outcome due to intermittent assessments, and left truncation in one study phase (ADNIGO). Specifically, we first develop a semiparametric transformation model on interval-censored and left-truncated data and estimate parameters through a sieve approach. Then we propose a computationally efficient generalized score test to identify variants associated with AD progression. Next, we implement a novel neural network on interval-censored data (NN-IC) to construct a prediction model using top variants identified from the genome-wide test. Comprehensive simulation studies show that the NN-IC outperforms several existing methods in terms of prediction accuracy. Finally, we apply the NN-IC to the full ADNI data and successfully identify subgroups with differential progression risk profiles. Data used in the preparation of this article were obtained from the ADNI database.
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