Applications of single-cell RNA sequencing in drug discovery and development
Bram Van de Sande, Joon Sang Lee, Euphemia Mutasa-Gottgens, Bartholomew J. Naughton, Wendi Bacon, Jonathan Manning, Yong Wang, Jack Pollard, Melissa G. Mendez, Jon Hill, Namit Kumar, Xiaohong Cao, Xiao Chen, Mugdha Khaladkar, Ji Wen, Andrew R. Leach, Edgardo A. Ferrán
Abstract
Single-cell technologies, particularly single-cell RNA sequencing (scRNA-seq) methods, together with associated computational tools and the growing availability of public data resources, are transforming drug discovery and development. New opportunities are emerging in target identification owing to improved disease understanding through cell subtyping, and highly multiplexed functional genomics screens incorporating scRNA-seq are enhancing target credentialling and prioritization. ScRNA-seq is also aiding the selection of relevant preclinical disease models and providing new insights into drug mechanisms of action. In clinical development, scRNA-seq can inform decision-making via improved biomarker identification for patient stratification and more precise monitoring of drug response and disease progression. Here, we illustrate how scRNA-seq methods are being applied in key steps in drug discovery and development, and discuss ongoing challenges for their implementation in the pharmaceutical industry. There have been significant recent advances in the development of single-cell technologies, providing remarkable opportunities for drug discovery and development. Here, Ferran and colleagues discuss how single-cell technologies, primarily single-cell RNA sequencing methods, are being applied in the drug discovery pipeline, from target identification to clinical decision-making. Ongoing challenges and potential future directions are discussed.