Comprehensive and Robust Tools for Analysis of Tumor Heterogeneity and Evolution

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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.