Single-cell DNA sequencing (scDNA-seq) enables decoding somatic cancer variation. Existing methods are hampered by low throughput or cannot be combined with transcriptome sequencing in the same cell. We propose HIPSD&R-seq (HIgh-throughPut Single-cell Dna and Rna-seq), a scalable yet simple and accessible assay to profile low-coverage DNA and RNA in thousands of cells in parallel. Our approach builds on a modification of the 10X Genomics platform for scATAC and multiome profiling. In applications to human cell models and primary tissue, we demonstrate the feasibility to detect rare clones and we combine the assay with combinatorial indexing to profile over 17,000 cells.

中文翻译：

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HIPSD&R-seq 支持可扩展的基因组拷贝数和转录组分析


单细胞 DNA 测序 （scDNA-seq） 能够解码体细胞癌变异。现有方法受到低通量的阻碍，或者无法与同一细胞中的转录组测序相结合。我们提出了 HIPSD&R-seq （HIgh-throughPut Single-cell DNA and Rna-seq），这是一种可扩展但简单易获得的检测方法，可同时分析数千个细胞中的低覆盖率 DNA 和 RNA。我们的方法建立在对 10X Genomics 平台的修改之上，用于 scATAC 和多组学分析。在人类细胞模型和原代组织的应用中，我们证明了检测稀有克隆的可行性，并将该检测与组合标定相结合，以分析超过 17,000 个细胞。