Information-theory-based benchmarking and feature selection algorithm improve cell type annotation and reproducibility of single cell RNA-seq data analysis pipelines

Single cell RNA sequencing (scRNA-seq) data are now routinely generated in experimental practice because of their promise to enable the quantitative study of biological processes at the single cell level. However, cell type and cell state annotations remain an important computational challenge in analyzing scRNA-seq data. Here, we report on the development of a benchmark dataset where reference annotations are generated independently from transcriptomic measurements. We used this benchmark to systematically investigate the impact on labelling accuracy of different approaches to feature selection, of different clustering algorithms, and of different sets of parameter values. We show that an approach grounded on information theory can provide a general, reliable, and accurate process for discarding uninformative features and to optimize cluster resolution in single cell RNA-seq data analysis.