Ultrascale Machine Learning to Empower Discovery in Alzheimers Disease Biobanks

摘要 对PAR-19-269“阿尔茨海默病遗传和表型数据的认知系统分析”的回应 (U01临床试验不允许）"，我们的项目联合了AD基因组学、机器学习和人工智能（包括 深度学习）、大规模数据集成和国际数据协调，以便在精心设计的 与NIH、ADSP和NIAGADS密切合作的联盟结构。我们将开发一套 用于阿尔茨海默病（AD）基因组的超大规模分析的互补大数据分析方法 和表型数据。阿尔茨海默病测序项目现在产生的大量数据 （ADSP），国家阿尔茨海默氏症协调中心（NACC），阿尔茨海默氏症神经影像学倡议（ADNI）， 加速药物合作伙伴AD（AMP-AD）和英国生物银行（UKBB）远远超过了所有 目前的分析方法没有跟上数据收集的规模和速度。该海量 遗传和表型数据的需求新的和更强大的算法：（1）存储，管理， 以不断增长的规模操纵全基因组序列和相关数据;（2）发现新的AD风险 通过合并信息学和AD基因组学数据库， ATN（v）生物标志物，现在定义生物AD。我们的超尺度机器学习计划，或“ULTRA” - 将提供新的人工智能和深度学习工具，以发现大规模基因组学数据的特征， 通过合并所有相关数据源，将基因组数据转化为生物标志物特征。我们经验丰富的PI团队将 协调美国各地的努力，以创建这些大规模的数据分析工具。我们的MPI团队和6 Core 领导者在开拓机器学习方面拥有数十年的合作经验，并与AD社区合作 AD遗传学和神经影像学方法，包括领导国际神经影像学联盟， 世界专用核心专注于基因组、成像和认知数据协调。精选数据将 然后有效地导入人工智能方法和信息学管道， 社区利用来自ADSP，NACC，ADNI， AMP-AD和其他。我们的工作是由一个精心设计和协调的财团组织的， AD基因组学和神经影像学领域的专家、临床领导者和先驱分析师。我们的超规模人工智能 工具将推进AD基因组学研究，并将包括培训工作和专门的药物再利用 核心这个团队的努力将加速对遗传、分子和神经生物学机制的理解。 AD，对疾病和药物开发产生重大的转化影响。

ABSTRACT In response to PAR-19-269 “Cognitive Systems Analysis of Alzheimer's Disease Genetic and Phenotypic Data (U01 Clinical Trial Not Allowed)”, our project unites experts in AD genomics, machine learning and AI (including deep learning), large-scale data integration, and international data harmonization to work in a carefully-designed Consortium Structure in close partnership with the NIH, ADSP, and NIAGADS. We will develop a suite of complementary big data analytic approaches for ultra-scale analysis of Alzheimer’s Disease (AD) genomic and phenotypic data. The vast data volumes now generated by the Alzheimer’s Disease Sequencing Project (ADSP), National Alzheimer’s Coordinating Center (NACC), Alzheimer’s Disease Neuroimaging Initiative (ADNI), Accelerating Medications Partnership AD (AMP-AD), and UK Biobank (UKBB), far exceed the capacity of all current analytic methods, which have not kept pace with the scale and speed of data collection. This vast amount of genetic and phenotypic data mandates new and more powerful algorithms to: (1) store, manage, and manipulate whole-genome sequences and associated data on an ever-growing scale; (2) discover novel AD risk and protective loci by merging informatics and AD genomics databases; (3) relate whole-genome changes to the ATN(v) biomarkers that now define biological AD. Our Ultrascale Machine Learning Initiative, or “ULTRA” - will offer new AI and deep learning tools to discover features in massive scale genomics data - relating whole genome data to biomarker features by merging all relevant data sources. Our team of experienced PIs will coordinate efforts across the U.S. to create these large-scale data analytic tools. Our MPI team and 6 Core Leads have decades of experience working together and with the AD community in pioneering machine learning methods for AD genetics and neuroimaging, including leadership of international neuroimaging consortia across the world. Dedicated Cores focus on Genomic, Imaging, and Cognitive Data Harmonization. Curated data will then be efficiently imported into AI approaches and informatics pipelines that will allow the AD research community to leverage ultra-scale, multidimensional genomic and phenotypic data from the ADSP, NACC, ADNI, AMP-AD, and others. Our work is organized by a carefully-designed and coordinated Consortium guided by all stake-holders, clinical leaders, and pioneering analysts in AD genomics and neuroimaging. Our ultrascale AI tools will advance AD genomics research and will include efforts in training, and a dedicated Drug Repurposing Core. This team effort will accelerate understanding of the genetic, molecular and neurobiological mechanisms of AD, yielding significant translational impact on disease and drug development.