Estimating the completeness of large-scale single-cell sequencing projects

During embryonic development, cells undergo differentiation into highly specialized cell types. Capitalizing on single-cell RNA sequencing, substantial resources have been invested to-wards cataloguing these differentiated cell types by their transcriptomic profiles. Despite the extensive efforts to profile various organs and their cellular compositions, we lack metrics to assess the completeness of the sequencing projects. In this cellular biodiversity analysis, we made use of the increasingly available single-cell data together with statistical methods, originally developed for assessing the species richness of ecological communities, to estimate the cellular diversity of any organ based on data from single-cell profiling technologies. Deriving from such cellular richness estimates, we established a statistical framework that allows assessment of the completeness of any large-scale single-cell profiling project, after which additional sequencing efforts do not anymore reveal new insights into an organ’s cellular composition. Such estimates can serve as stoppage-points for the ongoing single-cell sequencing projects, hence guiding more cost-efficient completion of the profiling on various human tissues.