Comprehensive and Robust Tools for Analysis of Tumor Heterogeneity and Evolution

用于分析肿瘤异质性和进化的全面而强大的工具

• 批准号: 10677268
• 负责人: Benjamin Raphael
• 金额: $ 8.1万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-24 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10677268
• 关键词: Alleles; Bar Codes; Biotechnology; Cells; Chromosome abnormality; Clonality; Collaborations; Collection; Computational algorithm; Computer software; Custom; DNA; DNA sequencing; Data; Data Analytics; Development; Diagnosis; Evolution; Genomic DNA; Genomic Instability; Genomics; Goals; Heterogeneity; Hodgkin Disease; Malignant Neoplasms; Maps; Measurement; Methods; Modeling; Molecular; Nature; Pattern; RNA; Research Personnel; Resolution; Sampling; Slide; Spatial Distribution; Technology; Time; Tissues; Transposase; Work; analytical tool; base; cancer diagnosis; cancer therapy; computational platform; computerized tools; genome sequencing; individual patient; neoplastic cell; novel; novel strategies; precision oncology; reconstruction; single cell sequencing; single-cell RNA sequencing; spatiotemporal; tool; transcriptome sequencing; treatment response; tumor; tumor heterogeneity; whole genome

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.

这是陈飞博士的IMAT项目（R33 CA 246455）和本博士之间的合作项目。 Raphael的ITCR项目（U24 CA 248453）。在这个项目中，我们将开发一个集成的 分析肿瘤中克隆的空间组织的实验和计算平台 样品该平台将联合收割机结合Slide-RNA-SeqV 2和Slide-DNA-seq技术 正在开发中的PI Chen的IMAT项目与定制的计算算法， 扩展PI Raphael的ITCR项目。拟议的工作有两个目标。在 在第一个目标中，我们将扩展和优化ITCR中正在开发的计算工具 确定肿瘤等位基因特异性拷贝数畸变和空间分布的项目 Slide-RNA-SeqV 2数据中的克隆产生了IMAT项目。在第二个目标中， 使用Slide-seq生成高分辨率空间DNA数据。这些数据将与 拉斐尔小组的计算算法表明，使用等位基因特异性拷贝 数目畸变导致肿瘤演变的重建比总数畸变更可靠。 10 X Genomics全基因组单细胞测序数据中的拷贝数。的组合 Slide-RNA-seq数据、Slide-DNA-seq数据和先进的计算方法将使 肿瘤内克隆的空间分布和时空分布的新研究 肿瘤演变的模式。