Statistical method scDEED for detecting dubious 2D single-cell embeddings and optimizing t-SNE and UMAP hyperparameters.

Two-dimensional (2D) embedding methods are crucial for single-cell data visualization. Popular methods such as t-distributed stochastic neighbor embedding (t-SNE) and uniform manifold approximation and projection (UMAP) are commonly used for visualizing cell clusters; however, it is well known that t-SNE and UMAP's 2D embeddings might not reliably inform the similarities among cell clusters. Motivated by this challenge, we present a statistical method, scDEED, for detecting dubious cell embeddings output by a 2D-embedding method. By calculating a reliability score for every cell embedding based on the similarity between the cell's 2D-embedding neighbors and pre-embedding neighbors, scDEED identifies the cell embeddings with low reliability scores as dubious and those with high reliability scores as trustworthy. Moreover, by minimizing the number of dubious cell embeddings, scDEED provides intuitive guidance for optimizing the hyperparameters of an embedding method. We show the effectiveness of scDEED on multiple datasets for detecting dubious cell embeddings and optimizing the hyperparameters of t-SNE and UMAP.