Abstract
Single-cell RNA sequencing (scRNA-seq) experiments often measure thousands of genes, making them high-dimensional data sets. As a result, dimensionality reduction (DR) algorithms such as t-SNE and UMAP are necessary for data visualization. However, the use of DR methods in other tasks, such as for cell-type detection or developmental trajectory reconstruction, is stymied by unquantified non-linear and stochastic deformations in the mapping from the high- to low-dimensional space. In this work, we present a statistical framework for the quantification of embedding quality so that DR algorithms can be used with confidence in unsupervised applications. Specifically, this framework generates a local assessment of embedding quality by statistically integrating information across embeddings. Furthermore, the approach separates biological signal from noise via the construction of an empirical null hypothesis. Using this approach on scRNA-seq data reveals biologically relevant structure and suggests a novel “spectral” decomposition of data. We apply the framework to several data sets and DR methods, illustrating its robustness and flexibility as well as its widespread utility in several quantitative applications.
Competing Interest Statement
The authors have declared no competing interest.
