Single-cell datasets are increasing in number and size. To leverage this rich resource, new workflows can reveal novel insights and discoveries. This perspective discusses the computational challenges and opportunities for single-cell reference-mapping algorithms that may eventually replace manual and laborious unsupervised clustering pipelines.

Nature Biotechnology, Published online: 25 May 2023; doi:10.1038/s41587-023-01767-yReference mapping is extended beyond scRNA-seq to single-cell epigenetic and proteomic data.