LINEAGE: Label-free identification of endogenous informative single-cell mitochondrial RNA mutation for lineage analysis

Significance Lineage analysis is an important assay for developmental biology, cancer biology, etc. Traditional tools in this field are time consuming, technically challenging, and in demand of preexisting knowledge. By integrating exogenous barcodes into cells, single-cell RNA-sequencing (scRNA-seq) can be used to conduct such tasks, but these assays required significant expertise in both wet- and dry-laboratory experiments. We developed a user-friendly algorithm to conduct cell-lineage inference solely based on endogenous markers of label-free scRNA-seq. This algorithm is able to identify lineage-informative mutations from a bunch of interfering mitochondrial RNA variants with high accuracy and efficiency. With this algorithm, we removed most of the technical hurdles of lineage analysis on scRNA-seq and will dramatically accelerate its application in biological research.