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.

项目摘要 在美国，阿尔茨海默氏病（AD）在65岁以上的人中约有10％ 并提取了全国的个人和财务损失。尽管数十年 那里的投资没有治愈和有效的治疗方法。促成因素 难度包括AD病因的复杂，多因素性质，可难治性地指导 临床观察，尤其是在早期阶段。 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 机械细节推动了诊所中AD的发展。这特别相关 今天，由于越来越多的共识，即A-Beta假设必须让位 这反映了AD的复杂，多因素的性质。幸运的是，诸如空间等新方法 生物学非常适合以AD的方式捕获蛋白质网络的复杂性 传统的组织学分析不能。但是不幸的是，应用空间的障碍 整个组织和器官中的生物学都是很大的，包括高昂的仪器成本， 技术复杂的工作流以及大量的数据管理，分析和可视化 挑战。 该建议将通过提供方便的费用服务平台来帮助消除这些障碍 可以将大脑发送成像和分析的地方。高价值区域的组织 可以快速识别并选择部分进行二级空间生物学分析。这 然后可以将分析的组织部分和3D数据集映射到其正确的位置 体内成像和脑图，例如艾伦CCF。重要的是，该项目将建立在 高性能的云平台可以处理多稳定的多路复用数据集并服务 他们有效地使研究人员可以轻松地比较对每个大脑区域的治疗效果 跨年龄，性别和小鼠模型的基础。 该提议扩大了以前的NIA提案的成功，该提议结合了来自 Tissuevision和NIA资助的Model-AD中心位于杰克逊实验室。建立 这种令人印象深刻的合作伙伴关系我们将增加Bruker，Inc。的科学制造商$ 2.4B 目前正在推进尖端空间生物学方法的乐器，特别是 MALDI-IHC，它将能够对组织数据集进行60+的PLEX成像。在 此外，西雅图退伍军人政府将协助我们的空间分析工作 成像其流体高温系统上的质量细胞仪。我们相信 下一代广告研究模型，先进的空间生物学仪器和数据 分析代表一个理想的联盟，有望提供极为有价值的集合 广告研究社区的新工具，最终可能为有效的广告开辟道路 治疗。