Deciphering single-cell gene expression variability and its role in drug response

Abstract

The effectiveness of drug treatments is profoundly influenced by individual responses, which are shaped by gene expression variability, particularly within pharmacogenes. Leveraging single-cell RNA sequencing (scRNA-seq) data, our study explores the extent of expression variability among pharmacogenes in a wide array of cell types across eight different human tissues, shedding light on their impact on drug responses. Our findings broaden the established link between variability in pharmacogene expression and drug efficacy to encompass variability at the cellular level. Moreover, we unveil a promising approach to enhance drug efficacy prediction. This is achieved by leveraging a combination of cross-cell and cross-individual pharmacogene expression variation measurements. Our study opens avenues for more precise forecasting of drug performance, facilitating tailored and more effective treatments in the future.