Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada.
Department of Statistics, University of British Columbia, Vancouver, British Columbia, Canada.
Genome Biol. 2019 Mar 12;20(1):54. doi: 10.1186/s13059-019-1645-z.
Measuring gene expression of tumor clones at single-cell resolution links functional consequences to somatic alterations. Without scalable methods to simultaneously assay DNA and RNA from the same single cell, parallel single-cell DNA and RNA measurements from independent cell populations must be mapped for genome-transcriptome association. We present clonealign, which assigns gene expression states to cancer clones using single-cell RNA and DNA sequencing independently sampled from a heterogeneous population. We apply clonealign to triple-negative breast cancer patient-derived xenografts and high-grade serous ovarian cancer cell lines and discover clone-specific dysregulated biological pathways not visible using either sequencing method alone.
单细胞分辨率下肿瘤克隆的基因表达测量将功能后果与体细胞改变联系起来。如果没有可扩展的方法来同时检测同一单细胞中的 DNA 和 RNA，那么必须对来自独立细胞群体的平行单细胞 DNA 和 RNA 测量进行映射，以进行基因组-转录组关联。我们提出了 clonealign，它使用独立于从异质群体中采样的单细胞 RNA 和 DNA 测序，为癌症克隆分配基因表达状态。我们将 clonealign 应用于三阴性乳腺癌患者来源的异种移植和高级别浆液性卵巢癌细胞系，并发现了仅使用一种测序方法无法发现的克隆特异性失调的生物学途径。
