Single-cell and imaging data integration software to spatially resolve the tumor microenvironment

项目摘要 肿瘤微环境（TME）在癌症进展和治疗反应中起着关键作用。新 单细胞和成像技术提供了前所未有的细胞类型组成、亚型 不同状态下的常见细胞类型，相邻细胞之间的相互作用以及T细胞功能。然而，在这方面， TME的这些组件中的每一个都由不同的测量技术捕获。着新的 用于多平台数据集成的计算方法和软件对于表征TME是必不可少的。 因此，我们提出了一个统一的R/Bioconductor包TMEMap，用于多平台单细胞数据 一体化目标1将整合单细胞RNA测序和单细胞TCR测序数据， 不同T细胞亚型和状态中的T细胞功能。目标2将整合组合单细胞RNA测序 CITE-seq中的蛋白质和成像蛋白质组学用于数字病理学，以绘制 TME。Aim 3将通过GenePattern Notebook进一步传播该软件。此工作流将 与临床研究者合作开发，以确保 使用来自协同研究的临床生物样本的可视化方法。总之，该软件将 为将来的工作提供了一个坚实的基础，将这些方法嵌入到多平台的数据库中， 在大规模NCI分析工作中， 人类肿瘤图谱网络

Project Summary The tumor microenvironment (TME) plays a critical role in cancer progression and therapeutic response. New single cell and imaging technologies provide unprecedented measurements of cell type composition, subtypes of common cell types in disparate states, interactions between neighboring cells, and T cell function. However, each of these components of the TME are captured by disparate measurement technologies. Both new computational methods and software for multi-platform data integration are essential to characterize the TME. Therefore, we propose a unified R/Bioconductor package TMEMap for multi-platform single cell data integration. Aim 1 will integrate single cell RNA-sequencing and single cell TCR-sequencing data to distinguish T cell function in distinct T cell subtypes and states. Aim 2 will integrate combined single cell RNA-sequencing and protein from CITE-seq with imaging proteomics for digital pathology to map cellular interactions in the TME. Aim 3 will further the disseminate this software with through GenePattern Notebook. This workflow will be developed in collaboration with clinical investigators to ensure usability and interpretability of the visualization methods using clinical biospecimens from synergistic studies. Altogether, this software will provide a strong foundation for future work embedding these methods in a database for multi-platform single cell data to automatically perform comprehensive TME characterization in large scale NCI profiling efforts such as the Human Tumor Atlas Network.