IsoSpark single cell proteomic and transcriptomic system for Keck Microarray Shared Resource (KMSR)

项目总结/摘要 凯克微阵列共享资源（KMSR）一直在提供尖端的下一代基因组学 技术，以支持数百个耶鲁和非耶鲁NIH资助的基础研究需求 investigators.最近，随着单细胞分离和条形码化技术的进步，微生物学领域的研究已经取得了很大进展。 单细胞基因组学/蛋白质组学和多组学已经开始提供前所未有的机会来分析DNA， mRNA和蛋白质在单细胞分辨率。自2016年以来，KMSR已成功地提供各种 单细胞服务，其中大部分使用10倍基因组学技术，专注于单细胞RNA测序 （scRNA-seq），其已被用于获得对细胞类型和状态的洞察。然而，这项技术仅 提供了与真实细胞功能低相关性的一个方面。联合收割机scRNA-seq的新分析方法 蛋白质组学分析已经在积极发展中。这将进一步揭示独特的见解， 更好地理解单细胞功能。 所要求的IsoSpark系统是一种独特的单细胞平台，能够实现高度多路复用的蛋白质组学， 转录组学分析。凭借新开发的Duomic芯片，IsoSpark正在成为第一个 整合单细胞功能蛋白质组学与转录组学，提供前所未有的见解， 转录组学和蛋白质组学之间的关系。 来自4个机构的27名研究人员支持我们为IsoSpark系统提供资金的请求， 理由他们建议使用所要求的系统来研究新的基于病毒的免疫基因疗法， COVID-19、帕金森病、肿瘤微环境、自身免疫性糖尿病 小脑神经变性、衰老、神经胶质瘤、胰腺癌和过渡期免疫失调 从急性肾损伤（阿基）到慢性肾脏病（CKD）。 此外，所要求的设备易于使用，具有成本效益，并有足够的吞吐量来支持 在本申请中引用的项目以及其他项目。这项建议的优点包括：（1）有效和 有效的集中设施，为极其多样化和富有成效的调查员用户群提供服务;（2）广泛的 PI的经验（3）KMSR有效整合尖端数据生产的能力 为数百名耶鲁大学和非耶鲁大学的研究人员的利益，和（4）广泛的基础设施 以及可用于使所请求的仪器在线并监督其连续使用的专业知识。 耶鲁大学在资本和机构人才方面进行了重大投资，以建设世界一流的基因组 该中心已被证明非常成功。所请求的工具将利用基础架构来确保 它的高价值和广泛的影响NIH资助的生物医学和基础研究内外耶鲁大学 社区

Project Summary/Abstract Keck Microarray Shared Resource (KMSR) has been providing cutting-edge next-generation genomics technologies to support the fundamental research needs of hundreds of Yale and non-Yale NIH-funded investigators. Most recently, with the advances in single-cell isolation and barcoding technologies, the field of single cell genomics/proteomics and multiomics has started offering unprecedented opportunities to profile DNA, mRNA, and proteins at a single-cell resolution. Since 2016, KMSR has been successfully providing a variety of single cell services, most of them using 10x genomics technology and focusing on Single-cell RNA sequencing (scRNA-seq), which has been used to gain insights into cell types and states. However, this technique only provided one facet with low correlation to true cellular function. New analysis methods that combine scRNA-seq with proteomic profiling has been in active development. This would further reveal unique insights and give a better understanding of single-cell function. The requested IsoSpark system is a unique single-cell platform enables highly multiplexed proteomic and transcriptomic analysis. With the newly developed Duomic chip, IsoSpark is becoming the first platform integrating single-cell functional proteomics with transcriptomics, providing unprecedented insights into the relation between transcriptomics and proteomics. Twenty-seven investigators from 4 institutions support our request for funding of IsoSpark system, with apt justifications. They propose to use the requested system to study novel viral based immune-gene therapy, immune dysregulation in COVID-19, Parkinson’s disease, Tumor Microenvironment, autoimmune diabetes, Cerebellar Neurodegeneration, aging, glioma, pancreatic cancer, and Immune Dysregulation during Transition from Acute Kidney Injury (AKI) to chronic kidney disease (CKD). Moreover, the requested equipment is easy to use and cost-effective and has sufficient throughput to support the projects cited in this application and beyond. The strengths of this proposal include; (1) an efficient and effective centralized facility serving an extremely diverse and productive investigator user base; (2) the extensive experience of the PI (3) the demonstrated ability of KMSR to effectively integrate cutting edge data production and analysis for the benefit of hundreds of Yale and non-Yale researchers, and (4) the extensive infrastructure and expertise that is available to bring the requested instrumentation on-line and to oversee its continuous use. Yale University has made a major investment in capital and institutional talent to build the world-class genomic center that has proven highly successful. The requested instrumentation will leverage the infrastructure to ensure its high value and broad impact on NIH-funded biomedical and basic research within and beyond the Yale community.