Prioritizing prognostic-associated subpopulations and individualized recurrence risk signatures from single-cell transcriptomes of colorectal cancer

Colorectal cancer (CRC) is one of the most common gastrointestinal malignancies. There are few recurrence risk signatures for CRC patients. Single-cell RNA-sequencing (scRNA-seq) provides a high-resolution platform for prognostic signature detection. However, scRNA-seq is not practical in large cohorts due to its high cost and most single-cell experiments lack clinical phenotype information. Few studies have been reported to use external bulk transcriptome with survival time to guide the detection of key cell subtypes in scRNA-seq data. We proposed scRank, a computational framework to prioritize prognostic-associated cell subpopulations based on within-cell relative expression orderings of gene pairs from single-cell transcriptomes. scRank achieves higher precision and concordance compared with five existing methods. Moreover, we developed single-cell gene pair signatures to predict recurrence risk for patients individually. Our work facilitates the application of the rank-based method in scRNA-seq data for prognostic biomarker discovery and precision oncology.