Persistent hindrances to data re-use in single-cell genomics

Abstract We report on our experience attempting to re-use published and publicly available single-cell (or single-nucleus) RNA-sequencing studies (scRNA-seq) from the Gene Expression Omnibus (GEO). We screened GEO for human, mouse and rat scRNA-seq studies as potential candidates for inclusion in the Gemma database of re-annotated and re-analyzed transcriptome studies. Using semi-automated and manual curation, we assessed whether GEO datasets included cell-level expression count matrices and cell-type annotations. We found that there are steep challenges to data reuse. Only ∼40% of studies provided readily usable processed count data that could be reliably mapped to GEO metadata, and fewer than 10% included author-provided cell-type annotations. While raw sequencing data were available for the majority of studies, only a small proportion could be re-analyzed automatically without reliance on heuristics. Our findings show that existing practices for single-cell RNA-sequencing data distribution and sharing are insufficient for effective reuse, and highlight the urgent need for repositories to strengthen and enforce submission requirements, particularly for processed data and cell-type annotations.