PT - JOURNAL ARTICLE AU - Mo Huang AU - Jingshu Wang AU - Eduardo Torre AU - Hannah Dueck AU - Sydney Shaffer AU - Roberto Bonasio AU - John Murray AU - Arjun Raj AU - Mingyao Li AU - Nancy R. Zhang TI - SAVER: Gene expression recovery for UMI-based single cell RNA sequencing AID - 10.1101/138677 DP - 2018 Jan 01 TA - bioRxiv PG - 138677 4099 - http://biorxiv.org/content/early/2018/03/08/138677.short 4100 - http://biorxiv.org/content/early/2018/03/08/138677.full AB - Rapid advances in massively parallel single cell RNA sequencing (scRNA-seq) is paving the way for high-resolution single cell profiling of biological samples. In most scRNA-seq studies, only a small fraction of the transcripts present in each cell are sequenced. The efficiency, that is, the proportion of transcripts in the cell that are sequenced, can be especially low in highly parallelized experiments where the number of reads allocated for each cell is small. This leads to unreliable quantification of lowly and moderately expressed genes, resulting in extremely sparse data and hindering downstream analysis. To address this challenge, we introduce SAVER (Single-cell Analysis Via Expression Recovery), an expression recovery method for scRNA-seq that borrows information across genes and cells to impute the zeros as well as to improve the expression estimates for all genes. We show, by comparison to RNA fluorescence in situ hybridization (FISH) and by data down-sampling experiments, that SAVER reliably recovers cell-specific gene expression concentrations, cross-cell gene expression distributions, and gene-to-gene and cell-to-cell correlations. This improves the power and accuracy of any downstream analysis involving genes with low to moderate expression.