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bioRxiv · 10.1101/2020.02.10.942607

Simultaneous Profiling of DNA Copy Number Variations and Transcriptional Programs in Single Cells using RNA-seq

Madipour-Shirayeh, A.·Erdmann, N.·Leung-Hagesteijn, C.·Neri, P.·Tagoug, I.·Tiedemann, R. E.
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Abstract

Chromosome copy number variations (CNVs) are a near-universal feature of cancer however their effects on cellular function are incompletely understood. Single cell RNA sequencing (scRNA-seq) can reveal cellular gene expression however cannot directly link this to CNVs. Here we report new normalization methods (RTAM1 and -2) for scRNA-seq that improve gene expression alignment between cells, enhancing gene expression comparisons and the application of scRNA-seq to CNV detection. We also report sciCNV, a pipeline for inferring CNVs from RTAM-normalized data. Together, these tools provide dual profiling of transcriptomes and CNVs at single-cell resolution, enabling exploration of the effects of cancer CNVs on cellular programs. We apply these tools to multiple myeloma (MM) and examine the cellular effects of cancer CNVs +8q. Consistent with prior reports, MM cells with +8q22-24 upregulate MYC, MYC-target genes, mRNA processing and protein synthesis, verifying the approach. Overall, we provide new tools for scRNA-seq that enable matched profiling of the CNV landscape and transcriptome of single cells, facilitate deconstruction of the effects of cancer CNVs on cellular reprogramming within single samples.

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Madipour-Shirayeh, A., Erdmann, N., Leung-Hagesteijn, C., Neri, P., Tagoug, I., Tiedemann, R. E.. 2020-02-11. Simultaneous Profiling of DNA Copy Number Variations and Transcriptional Programs in Single Cells using RNA-seq. https://doi.org/10.1101/2020.02.10.942607

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