Comprehensive and Robust Tools for Analysis of Tumor Heterogeneity and Evolution

这是陈飞博士的IMAT项目(R33CA246455)与Ben博士的合作项目 拉斐尔的ITCR项目(U24CA248453)。在这个项目中，我们将开发一个集成的 分析肿瘤克隆空间组织的实验和计算平台 样本。该平台将结合Slide-RNA-SeqV2和Slide-DNA-Seq技术 在PiChen的IMAT项目中正在开发定制的计算算法 在皮拉斐尔的ITCR项目中扩展工作。拟议的工作有两个目标。在……里面 第一个目标，我们将扩展和优化ITCR中正在开发的计算工具 确定肿瘤的等位基因特异性拷贝数异常和空间分布的项目 Slide-RNA-SeqV2数据中的克隆生成了IMAT项目。在第二个目标中，皮晨将 使用Slide-seq生成高分辨率的空间DNA数据。该数据将唯一地与 来自拉斐尔小组的计算算法，他展示了使用等位基因特异性复制 数目像差导致的肿瘤进化重建比总体重建可靠得多 10倍基因组全基因组单细胞测序数据中的拷贝数。这两种技术的结合 Slide-RNA-seq数据、Slide-DNA-seq数据和先进的计算方法将使 克隆在肿瘤内的空间分布和时空分布的新研究 肿瘤进化的模式。

This is a collaborative project between Dr. Fei Chen’s IMAT project (R33CA246455) and Dr. Ben Raphael’s ITCR project (U24CA248453). In this project, we will develop an integrated experimental and computational platform to analyze the spatial organization of clones in tumor samples. This platform will combine the Slide-RNA-SeqV2 and Slide-DNA-seq technologies under development in PI Chen’s IMAT project with customized computational algorithms that extend the work in PI Raphael’s ITCR project. The proposed work is organized in two aims. In the first aim, we will extend and optimize computational tools under development in the ITCR project to identify allele-specific copy number aberrations and spatial distribution of tumor clones in Slide-RNA-SeqV2 data generated the IMAT project. In the second aim, PI Chen will generate high resolution spatial DNA data using Slide-seq. This data will uniquely integrate with computational algorithms from the Raphael group who showed that using allele-specific copy number aberrations led to much more reliable reconstructions of tumor evolution than total copy numbers in 10X Genomics whole-genome single-cell sequencing data. The combination of Slide-RNA-seq data, Slide-DNA-seq data and advanced computational approaches will enable novel studies of the spatial distribution of clones within tumors and the spatiotemporal patterns of tumor evolution.