Molecular Cross-Validation for Single-Cell RNA-seq
Batson, J.; Royer, L. A.; Webber, J. T.
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Single-cell RNA sequencing enables researchers to study the gene expression of individual cells. However, in high-throughput methods the portrait of each individual cell is noisy, representing thousands of the hundreds of thousands of mRNA molecules originally present. While many methods for denoising single-cell data have been proposed, a principled procedure for selecting and calibrating the best method for a given dataset has been lacking. We present \"molecular cross-validation,\" a statistically principled and data-driven approach for estimating the accuracy of any denoising method without the need for ground-truth. We validate this approach for three denoising methods--principal component analysis, network diffusion, and a deep autoencoder--on a dataset of deeply-sequenced neurons. We show that molecular cross-validation correctly selects the optimal parameters for each method and identifies the best method for the dataset.
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