How many markers are needed to robustly determine a cell's type?

Our understanding of cell types has advanced considerably with the publication of single-cell atlases. Marker genes play an essential role for experimental validation and computational analyses such as physiological characterization, annotation, and deconvolution. However, a framework for quantifying marker replicability and selecting replicable markers is currently lacking. Here, using high-quality data from the Brain Initiative Cell Census Network (BICCN), we systematically investigate marker replicability for 85 neuronal cell types. We show that, due to dataset-specific noise, we need to combine 5 datasets to obtain robust differentially expressed (DE) genes, particularly for rare populations and lowly expressed genes. We estimate that 10 to 200 meta-analytic markers provide optimal downstream performance and make available replicable marker lists for the 85 BICCN cell types. Replicable marker lists condense interpretable and generalizable information about cell types, opening avenues for downstream applications, including cell type annotation, selection of gene panels, and bulk data deconvolution.

Automated summary

Analysis utilizing high-quality data systematically researched the replicability of markers for 85 neuronal cell types; Combining multiple datasets is necessary due to dataset-specific noise for obtaining robust differentially expressed genes; Meta-analytic markers offer optimal downstream performance and provide replicable marker lists for the 85 BICCN cell types.