Designing circulating-tumor cells (CTCs) detection method using co-measurement data of single-cell RNA and targeted DNA sequencing

Abstract

Detection of cancer for diagnosis and tracking the prognosis of the patients using liquid biopsy procedure: the extraction of blood for the detection of cells is the least invasive procedure and relatively fast process compared to tissue biopsy, which would make the isolation and analysis of biological samples like exosomes, circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), a preferred approach over solid biopsy via open surgery. Due to the sparsity of the overall count of CTCs in the blood and low genomic content recovery from them, it is hard to identify and characterize CTCs to make insights into the biology of the disease. In this study, we analyzed the concurrent data of single-cell RNA-seq and targeted DNA-seq from 9 pancreatic cancer patients. We developed a pipeline that leverages the nature of concurrent data to identify CTCs from non-CTCs (blood cells). We were able to identify CTCs using the mutation profile and transcriptomic profiles of CTCs. We made fundamental biological insights into pancreatic cancer disease by integrating mutational and transcriptomic profiles of the cells.