A high throughput multiplexed pipeline for models of Alzheimer’s Disease

用于阿尔茨海默病模型的高通量多重管道

• 批准号: 10766665
• 负责人: Timothy M. Ragan
• 金额: $ 124.9万
• 依托单位: TISSUEVISION, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-15 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10766665
• 关键词: 3-Dimensional; Affect; Age; Alzheimer disease screening; Alzheimer' s Disease; Alzheimer' s disease model; Alzheimer' s disease therapy; Atlases; Automobile Driving; Back; Biological Sciences; Biology; Brain; Brain Mapping; Brain imaging; Brain region; Cells; Cellular biology; Client; Clinic; Clinical; Cloud Computing; Collaborations; Communities; Complex; Consensus; Cytometry; Data; Data Analyses; Data Set; Development; Dimensions; Ensure; Etiology; Fee-for-Service Plans; Fluorescence; Funding; Histologic; Image; Image Analysis; Image Cytometry; Imaging technology; Indiana; Investments; Label; Location; Manufacturer; Maps; Methods; Modeling; Molecular; Multimodal Imaging; Mus; Nature; Nerve Degeneration; Neurosciences; Organ; Output; Performance; Persons; Pharmacologic Substance; Phase; Proteins; Proteomics; Publications; Publishing; Refractory; Research; Research Contracts; Research Personnel; Resources; Sampling; Series; Services; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Speed; System; Techniques; Technology; The Jackson Laboratory; Therapeutic Intervention; Tissue imaging; Tissues; United States; United States Department of Veterans Affairs; Universities; Visualization; analysis pipeline; base; brain research; cell type; clinical translation; cloud based; cloud platform; cost; data management; data visualization; deep learning; effective therapy; high resolution imaging; human old age (65+); imaging approach; in vivo imaging; indexing; instrument; instrumentation; interest; mouse model; multiphoton imaging; multiple omics; nano-string; next generation; novel; sex; success; synergism; terabyte; three-dimensional modeling; tool; transcriptomics; treatment comparison; treatment effect; treatment group; two-photon

PROJECT SUMMARY Alzheimer’s disease (AD) affects roughly 10% of people over the age of 65 in the United States and extracts an enormous personal and financial toll on the nation. Despite decades of investment there exists no cure nor effective treatment. Contributing factors behind the difficulty include the complex, multifactorial nature of AD etiology that is refractory to direct clinical observation especially in its early stages. As such, research models are of paramount importance as they hold great potential to reveal key mechanistic details driving the progression of AD in the clinic. This is of particular relevance today as there is a growing consensus that the A-Beta hypothesis must give way to approaches that reflect the complex, multifactorial nature of AD. Fortunately, new methods such as spatial biology are well suited to capture the complexity of protein networks implicated in AD in ways that traditional histological analysis cannot. Unfortunately, however, barriers to apply spatial biology in whole tissues and organs are substantial, including high cost of instrumentation, technically complex workflows, and substantial data management, analysis, and visualization challenges. This proposal will help eliminate these barriers by offering a convenient fee-for-service platform where brains can be sent to be imaged and analyzed. High value region-of-interest tissue sections can be quickly identified and selected for secondary spatial biology analyses. The analyzed tissue sections and 3D datasets can then be mapped back to their correct location in in vivo imaging and brain atlases such as the Allen CCF. Importantly, this project will be built on a high-performance cloud platform that can handle multi-terabyte multiplexed datasets and serve them efficiently such that researchers can easily compare treatment effects on a per brain region basis across age, sex, and mouse model. This proposal extends the success of a previous NIA proposal that combined teams from TissueVision and the NIA-funded MODEL-AD Center at The Jackson Laboratory. To build on this impressive partnership we will be adding Bruker, Inc. a $2.4B manufacturer of scientific instruments that is currently advancing cutting-edge spatial biology approaches, notably MALDI-IHC, which will be capable of performing a 60+ plex imaging of tissue datasets. In addition, the Seattle Veteran’s Administration will be assisting our spatial profiling efforts with Imaging Mass Cytometry on its Fluidigm Hyperion system. We believe the synergy between next-generation AD research models, advanced spatial biology instrumentation and data analysis represents an ideal alliance that holds the promise to deliver an extremely valuable set of new tools to the AD research community that may finally open the way for effective AD treatments.

项目总结 在美国，大约10%的65岁以上的人患有阿尔茨海默病(AD) 并给国家带来巨大的个人和经济损失。尽管几十年来 投资在那里既没有治愈的方法，也没有有效的治疗方法。背后的促成因素 困难包括AD病因学的复杂、多因素性质，难以直接 临床观察，尤其是早期临床观察。 因此，研究模型至关重要，因为它们具有揭示关键的巨大潜力 在临床上推动阿尔茨海默病进展的机制细节。这一点特别重要。 今天，随着越来越多的人达成共识，A-Beta假说必须让位于 这反映了AD的复杂、多因素的本质。幸运的是，新的方法，如空间 生物学非常适合于捕捉与AD有关的蛋白质网络的复杂性 传统的组织学分析做不到的。然而，不幸的是，应用空间的障碍 整个组织和器官中的生物学是大量的，包括高昂的仪器成本， 技术复杂的工作流程，以及大量数据管理、分析和可视化 挑战。 这项提议将通过提供一个方便的收费服务平台来帮助消除这些障碍 大脑可以被送到那里进行成像和分析。高价值感兴趣区组织 可以快速识别和选择切片以进行二次空间生物学分析。这个 然后，可以将分析的组织切片和3D数据集映射回其在中的正确位置 活体成像和脑图谱，如艾伦CCF。重要的是，这个项目将建立在 高性能云平台，可处理数TB的多路传输数据集和服务 这样研究人员就可以很容易地比较每个大脑区域的治疗效果 基于年龄、性别和小鼠模型。 这项提案延续了NIA之前的一项提案的成功，该提案将来自 TisseVision和NIA资助的模型-杰克逊实验室的AD中心。在此基础上继续发展 这一令人印象深刻的合作伙伴关系我们将增加布鲁克公司，一家价值24亿美元的科学技术制造商 目前正在推进尖端空间生物学方法的仪器，特别是 MALDI-IHC，它将能够对组织数据集执行60多个复数成像。在……里面 此外，西雅图退伍军人管理局将协助我们的空间侧写工作 在其Fluidigm Hyperion系统上进行成像质谱分析。我们相信两者之间的协同效应 下一代AD研究模型、先进的空间生物学仪器和数据 分析代表了一种理想的联盟，它承诺提供一套极其有价值的产品 向AD研究社区提供新的工具，最终可能为有效的AD开辟道路 治疗。