Single-cell genomics has become a mainstay technology used to dissect multicellular organisms and tissues that are composed of cells with diverse functions. The use of single-cell technology in cancer is especially important, as the heterogeneity of tumor cell composition and regulatory mechanisms that afford tumor cells with abilities such as drug resistance or immune evasion are elusive and cannot be resolved with traditional bulk approaches. Evidently, both the genomic and transcriptomic heterogeneity of tumors contributes to the disease, and understanding the importance of both the transcriptome and the genome in cancer studies is crucial. Therefore, the next wave of single-cell genomics would be integrating multiple-omic to comprehensively understand the cellular behaviors...[ Read more ]

Single-cell genomics has become a mainstay technology used to dissect multicellular organisms and tissues that are composed of cells with diverse functions. The use of single-cell technology in cancer is especially important, as the heterogeneity of tumor cell composition and regulatory mechanisms that afford tumor cells with abilities such as drug resistance or immune evasion are elusive and cannot be resolved with traditional bulk approaches. Evidently, both the genomic and transcriptomic heterogeneity of tumors contributes to the disease, and understanding the importance of both the transcriptome and the genome in cancer studies is crucial. Therefore, the next wave of single-cell genomics would be integrating multiple-omic to comprehensively understand the cellular behaviors and the interplay of molecules within the genome, transcriptome, and other layers. Here, we introduce a novel single-cell DNA and RNA co-amplification method, scONE-seq, which enables co-profiling of the transcriptome and genome from the same single cell or nucleus in a one-tube reaction. We demonstrate the utility of scONE-seq, by first benchmarking our method against existing methods using various sample types, including several cell lines and lymphocytes from the blood of a healthy donor. Furthermore, we were able to identify a very rare clone in a frozen IDH1-Mutant glioblastoma (GBM) sample that was only distinguishable by simultaneous classification of clonal and transcriptomic information, and further analysis of RNA and DNA profiles of this clone suggests that this rare clone may play a role in the supporting of the tumor, as well as regulate the tumor’s interactions with neighboring normal cells in its microenvironment.