Abstract:
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With the recent advancements in single-cell RNA sequencing (scRNA-seq), solid simulation methods for scRNA-seq data are required to develop reliable analysis methods. However, due to the noisy nature of scRNA-seq data, current available simulation methods cannot sufficiently capture and simulate important properties of real data, especially the biological variation. In this study, we developed SCRIP, a novel simulator for scRNA-seq data. SCRIP adopted a zero inflated Gamma-Poisson hierarchical model and enabled the simulation of various inherent characteristics of scRNA-seq data including biological dispersion, transcriptional bursting and drop-out event. SCRIP improved scRNA-seq data simulation by incorporating mean-variance dependency via generalized additive model. Also, SCRIP enabled the simulation of bursting effect based on Beta-Poisson mixture distribution. Compared to existing simulators, SCRIP showed a significantly higher accuracy of stimulating key data features including mean-variance dependency in all experiments. SCRIP also outperformed 5 existing methods in capturing between-cell type variation and recovering cell trajectories.
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