Single-Cell mRNA Sequencing in Precision Medicine: Promise and Challenges

Ke K. Zhang, Jiangyuan Li, Minsun Jeon, Kenneth S. Ramos

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Thanks to the fast advancement of high throughput biotechnology, especially next generation sequencing, precision medicine has made tremendous progress by providing personalized medical advice and designing targeted treatment regimes for disease prevention and therapy. However, the onset and progression of complex human diseases, such as cancer and cardiovascular diseases, are often multifactorial and multi-trajectory, leading to cellular heterogeneity and molecular complexity that increase drug tolerance and resistance. Effective precision medicine requires the characterization and quantification of molecular variations at single-cell resolution to account for such heterogeneity. In the last few years, the rapid development of single-cell sequencing technology has made it possible to obtain high throughput profiling of the genome, transcriptome, and epigenome of individual cells, enabling the classification and quantification of cell subpopulations and revealing cellular variations of molecular levels and interactions. Thus, combinatory drug treatment can be designed based on the knowledge of heterogeneous cellular compositions and molecular events, ensuring effectively personalized therapy. Nevertheless, as developing technology, single-cell sequencing has technical difficulties and informatics challenges that prevent it from the widespread utility in precision medicine. Accounting for the diversity of genomic information across cells requires rigorous experimental design, the successful harvest of viable cells, enrichment of genomic information, and robust bioinformatic analysis. This chapter introduces the recent technical advancement of single-cell sequencing, discusses its utility and limitations for single-cell research, and presents its promises and challenges for applications in precision medicine in cancer, cardiovascular diseases, birth defects, metabolic syndrome, and immune disorders.

Original languageEnglish (US)
Title of host publicationComprehensive Precision Medicine, First Edition, Volume 1-2
PublisherElsevier
Pages59-72
Number of pages14
Volume2
ISBN (Electronic)9780128240106
DOIs
StatePublished - 2024

Keywords

  • Batch effects
  • Clustering
  • Data normalization
  • Drop-seq
  • Microwell-seq
  • Precision medicine
  • Single-cell sequencing
  • Trajectory analysis
  • scRNA-seq

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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