Assessing Alzheimer disease risk and heterogeneity using multimodal machine learning approaches

项目总结/摘要 阿尔茨海默病（AD）是最常见的痴呆形式，其特征在于认知功能的进行性丧失， 功能不幸的是，目前还没有有效的治疗AD的方法，并且AD的临床干预措施还没有得到有效的治疗。 尽管付出了巨大的努力，但基本上还是失败了。对于当前的应用，我们寻求开发多模态机器 最近，通过利用丰富的AD相关组学数据和表型数据来学习模型， 从大规模的合作项目，如阿尔茨海默病神经成像倡议（ADNI）， 加速药物伙伴关系-AD（AMP-AD）和阿尔茨海默病测序项目（ADSP）。 在本申请中将追求三个目标。目标1。我们将建立一个可扩展的多式联运 无监督机器学习框架来研究AD异质性。由于多因素的性质， AD，我们将通过利用跨多个数据谱的丰富信息来执行AD子类型。目标二。 我们将建立一个可扩展的多模态监督机器学习框架，以量化AD风险， 对认知功能正常的老年人进行纵向随访。这些模型将从遗传易感性和基因 调节信息以及当参与者认知正常时测量的内表型。目标3： 我们将在死后人脑样本中构建AD相关基因相互作用网络。我们会研究 将多个组学数据与大脑样本中的AD相关联，并建立组织特异性相互作用网络， 了解AD发病机制的潜在分子机制。本申请代表 从临床和遗传风险因素中识别AD高风险个体的创新方法， 种族多样的人口。概述的策略将为风险分层提供新见解， AD的预防策略。我们还承诺通过GitHub或CRAN分享我们的方法，以供免费访问 在科学界。

PROJECT SUMMARY/ABSTRACT Alzheimer's disease (AD) is the most common form of dementia characterized by progressive loss of cognitive function. Unfortunately, currently there is no effective treatment for AD and clinical interventions of AD have largely failed despite enormous efforts. For the current application, we seek to develop multimodal machine learning models by leveraging the rich collection of AD-related omics data and phenotypical data recently generated from large-scale collaborative projects such as Alzheimer Disease Neuroimaging Initiative (ADNI), Accelerating Medicines Partnership-AD (AMP-AD) and the Alzheimer's Disease Sequencing Project (ADSP). Three aims will be pursued in the current application. Aim 1. We will build an expandable multimodal unsupervised machine learning framework to investigate AD heterogeneity. Given the multifactorial nature of AD, we will perform AD subtyping by harnessing the rich information across multiple spectrum of data. Aim 2. We will build an expandable multimodal supervised machine learning framework to quantify AD risk from longitudinal follow up of cognitively normal elders. The models will be built from genetic susceptibility and gene regulatory information as well as endophenotypes measured when participants were cognitive normal. Aim 3. We will build AD-related gene interaction networks in post-mortem human brain samples. We will examine the association of multiple omics data with AD in brain samples, and build tissue-specific interaction networks to understand potential molecular mechanisms underlying AD pathogenesis. The present application represents an innovative approach to identify individuals at high risk of AD from both clinical and genetic risk factors in ethnically diverse populations. The outlined strategy will provide new insights into the risk stratification and prevention strategies for AD. We also commit to share our methods through GitHub or CRAN for free access across the scientific community.