Single-cell analysis tools for drug discovery and development

• Published in: Nature reviews. Drug discovery Vol. 15; no. 3; pp. 204 - 216
• Main Authors: Heath, James R., Ribas, Antoni, Mischel, Paul S.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2016; Nature Publishing Group
• Subjects: 631/154; 631/337/2019; 631/337/475; 631/61/212; 631/67/1059/2325; Animals; Biomedicine; Biotechnology; Cancer Research; Drug discovery; Drug Discovery - methods; Drug Discovery - trends; Genomics - methods; Genomics - trends; Humans; Innovations; Medicinal Chemistry; Molecular Medicine; Oncology; Pharmacology/Toxicology; Proteomics - methods; Proteomics - trends; review-article; Single-Cell Analysis - methods; Single-Cell Analysis - trends
• ISSN: 1474-1776; 1474-1784
• DOI: 10.1038/nrd.2015.16

Key Points The recent significant advances in the development of single-cell analytical tools have enabled increasingly deep cellular analyses at the genomic, transcriptomic and proteomic levels. Genomic and transcriptomic methods utilize next-generation sequencing technologies, which complement protocols for improved quantification and cost-effective analyses of statistically significant numbers of single cells. Single-cell proteomics methods range from cytometry tools to microchip platforms. All these methods rely on antibodies, but different platforms yield different levels of quantification. Single-cell analyses reveal biology that is masked when cell populations or tissues are analysed. Illustrative examples include tracing the lineage of diseased cells back to the healthy tissue of origin, or a deep analysis of how targeted inhibitors can alter the structure of signalling pathways. Single-cell analysis tools are already playing important parts in drug discovery, particularly in the rapidly emerging field of cancer immunotherapy. Single-cell analysis tools are rapidly evolving, enabling cellular analyses at the genomic, transcriptomic and proteomic levels. Here, Heath and colleagues provide an overview of recently developed single-cell analysis technologies, discuss their biological applications and highlight their potential uses in drug discovery and development, focusing on the field of oncology. The genetic, functional or compositional heterogeneity of healthy and diseased tissues presents major challenges in drug discovery and development. Such heterogeneity hinders the design of accurate disease models and can confound the interpretation of biomarker levels and of patient responses to specific therapies. The complex nature of virtually all tissues has motivated the development of tools for single-cell genomic, transcriptomic and multiplex proteomic analyses. Here, we review these tools and assess their advantages and limitations. Emerging applications of single cell analysis tools in drug discovery and development, particularly in the field of oncology, are discussed.