Core 2: Tissue Imaging and Profiling Core

核心 2：组织成像和分析核心

• 批准号: 10526107
• 负责人: Rong Fan
• 金额: $ 36.94万
• 依托单位: INSTITUTE FOR SYSTEMS BIOLOGY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-22 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10526107
• 关键词: ATAC-seq; Address; Algorithms; Antibodies; Archives; Bar Codes; Cell Nucleus; Cells; ChIP-seq; Clinical; Combination immunotherapy; Computer Analysis; Computer software; Cost efficiency; DNA; Data; Data Analytics; Data Set; Epigenetic Process; Fluorescence; Fluorescent Antibody Technique; Freezing; Genes; Image; Image Analysis; Immune; Individual; Kinetics; Label; Location; Methods; Modeling; Names; Pathologic; Patients; Pattern; Population; Proteins; Proteome; Proteomics; Registries; Reporting; Research; Research Personnel; Resolution; Resources; Running; Scientist; Series; Slice; Specimen; Stains; System; Systems Biology; Techniques; Technology; Time; Tissue imaging; Tissues; Training; Training Programs; Transcript; Tumor Tissue; Validation; biobank; cancer cell; cost effective; data warehouse; digital; epigenetic profiling; experience; fluorescence imaging; genome-wide; high throughput analysis; human tissue; image processing; imaging informatics; inhibitor; innovation; interest; kinetic model; mouse model; multiple omics; nano-string; next generation sequencing; operation; preservation; programs; prospective; spatiotemporal; technology development; tool; transcriptome; tumor

Core 2. Imaging and Spatial Profiling Core Project Summary: Central technologies of the ST-Analytics U54 program are tissue imaging and profiling platforms, including two sets of tools for highly multiplex, multi-omic analysis of tumor tissue specimens including clinical archival FFPE and lightly preserved frozen tissues, and associated image analysis & informatics software. These Core resource technologies are used extensively by both ST Analytics Projects. The first spatial profiling tool is the well-established commercial Nanostring Digital Spatial Profiling (DSP) system, which permits analysis of regions of interest (ROIs) containing as few as 10-20 cells for detecting around 1000 genes or around 50 proteins (Lee 2017, Lu 2021). Adjacent slices from an FFPE block are prepared. The first is subjected to H&E staining for pathological analysis, while the second is stained with fluorescent antibodies to identify ROIs (for example, immune cell rich or cancer cell rich regions). Those ROIs are then interrogated at the transcriptome or proteome level. We have extensive experience with this tool for analysis of FFPE preserved patient tumor tissues (Lu 2021). The second profiling tools are those recently developed and reported by the Fan group (Deng 2021, 2021, Liu 2020). These powerful tools permit highly multiplex (up to 300-plex) proteomics and genome--wide transcriptome mapping at a resolution of 10 micrometers in tissue slices prepared from FFPE blocks. They also permit spatially resolved ATAC-seq and ChIP-seq type epigenetic profiling (Chen 2017; Chen 2018) at a similar spatial resolution in lightly fixed tissue slices. In particular, this epigenetic profiling capacity is unique to these tools. Similar to DSP, adjacent tissue slices can be H&E stained, and low-plex fluorescent imaging can be employed on the same slice for identification of nuclei as well as immune rich and immune poor regions for alignment validation. These methods can enable high throughput and cost-effective profiling of tissues, and some technology development to that end is described. The Core will continue to develop new spatial profiling tools to meet the emergent needs in the two projects as they advance in the next 5 years, thus serving as a Technoloy Innovation Hub for the U54 center and for the CSBC consortium as well.

核心2。成像和空间分析核心项目摘要： St-Analytics U54程序的中心技术是组织成像和分析平台，包括两个 用于肿瘤组织标本的高度多重多词分析的工具集，包括临床档案FFPE 以及易于保存的冷冻组织，以及相关的图像分析和信息学软件。这些核心 两个ST Analytics项目都广泛使用了资源技术。 第一个空间分析工具是建立了良好的商业纳米弦数字空间分析（DSP） 系统，允许分析感兴趣区域（ROI），其中包含10-20个单元的系统检测 1000个基因或大约50种蛋白质（Lee 2017，Lu 2021）。从FFPE块中制备了相邻切片。这 首先对H＆E进行病理分析进行H＆E染色，而第二种则用荧光抗体染色 识别ROI（例如，富含免疫细胞或富含癌细胞的免疫细胞区域）。然后在 转录组或蛋白质组水平。我们在此工具上有丰富的经验，用于分析FFPE保留 患者肿瘤组织（LU 2021）。 第二个分析工具是粉丝组最近开发和报告的工具（邓2021， 2021年，刘2020）。这些功能强大的工具允许高度多重（最多300个）蛋白质组学和基因组 - 范围内 从FFPE块制备的组织切片中的10微米分辨率的转录组映射。他们也是 允许在空间解决ATAC-SEQ和CHIP-SEQ型表观遗传分析（Chen 2017; Chen 2018）以类似 轻度固定组织切片中的空间分辨率。特别是，这种表观遗传分析能力是这些独有的 工具。与DSP相似，可以对邻近的组织切片进行H＆E染色，而低音荧光成像可以是 在同一切片上用于识别核以及免疫富含免疫和免疫区域 对齐验证。这些方法可以使组织的高吞吐量和成本效益分析，以及 描述了一些技术开发。核心将继续发展新的空间分析 在未来5年内发展时，可以满足两个项目的新兴需求的工具，从而充当 U54中心和CSBC财团的Technoloy Innovation Hub。