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CgCorrect: A method to correct for confounding cell-cell variation due to cell growth in single-cell transcriptomics.

Phys. Biol. 14:036001 (2017)
Publishers Version Postprint DOI
Open Access Green
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as soon as is submitted to ZB.
MOTIVATION: Accessing gene expression at the single cell level has unraveled often large heterogeneity among seemingly homogeneous cells, which remained obscured in traditional population based approaches. The computational analysis of single-cell transcriptomics data, however, still imposes unresolved challenges with respect to normalization, visualization and modeling the data. One such issue are differences in cell size, which introduce additional variability into the data, for which appropriate normalization techniques are needed. Otherwise, these differences in cell size may obscure genuine heterogeneities among cell populations and lead to overdispersed steady-state distributions of mRNA transcript numbers. RESULTS: We present cgCorrect, a statistical framework to correct for differences in cell size that are due to cell growth in single-cell transcriptomics data. We derive the probability for the cell growth corrected mRNA transcript number given the measured, cell size dependent mRNA transcript number, based on the assumption that the average number of transcripts in a cell increases proportional to the cell's volume during cell cycle. cgCorrect can be used for both data normalization, and to analyze steady-state distributions used to infer the gene expression mechanism. We demonstrate its applicability on both simulated data and single-cell quantitative real-time PCR data from mouse blood stem and progenitor cells and to quantitative single-cell RNA-sequencing data obtained from mouse embryonic stem cells. We show that correcting for differences in cell size affects the interpretation of the data obtained by typically performed computational analysis.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Cell Growth ; Computational Biology ; Single Cell Gene Expression; Stochastic Gene-expression; Rna-seq; Noise; Cycle; Pcr; Resolution; Networks; Stem
Reviewing status