Accurate denoising of single-cell RNA-Seq data using unbiased principal component analysis

Abstract Single-cell RNA-Seq measurements are commonly affected by high levels of technical noise, posing challenges for data analysis and visualization. A diverse array of methods has been proposed to computationally remove noise by sharing information across similar cells or genes, however their respective accuracies have been difficult to establish. Here, we propose a simple denoising strategy based on principal component analysis (PCA). We show that while PCA performed on raw data is biased towards highly expressed genes, this bias can be mitigated with a cell aggregation step, allowing the recovery of denoised expression values for both highly and lowly expressed genes. We benchmark our resulting ENHANCE algorithm and three previously described methods on simulated data that closely mimic real datasets, showing that ENHANCE provides the best overall denoising accuracy, recovering modules of co-expressed genes and cell subpopulations. Implementations of our algorithm are available at https://github.com/yanailab/enhance.