Single Cell Multi-Omics Technology: Methodology and Application

Abstract

In the era of precision medicine, multi-omics approaches enable the integration of data from diverse omics platforms, providing multi-faceted insight into the interrelation of these omics layers on disease processes. Single cell sequencing technology can dissect the genotypic and phenotypic heterogeneity of bulk tissue and promises to deepen our understanding of the underlying mechanisms governing both health and disease. Through modification and combination of single cell assays available for transcriptome, genome, epigenome, and proteome profiling, single cell multi-omics approaches have been developed to simultaneously and comprehensively study not only the unique genotypic and phenotypic characteristics of single cells, but also the combined regulatory mechanisms evident only at single cell resolution. In this review, we summarize the state-of-the-art single cell multi-omics methods and discuss their applications, challenges, and future directions.

Keywords: epigenetics; gene regulation; single cell epigenome; single cell multi-omics profiling; single cell proteome; single cell transcriptome.

Figure 1

Timeline of single cell sequencing methods milestones.

Figure 2

Strategies for multi-omics profiling of single cells. Three major types of molecules relating to biological central dogma (Top). Single cell genomics methods profiling the genome, epigenome, transcriptome, and proteome are shown by different shapes with variable colors (Middle). Single cell multi-omics methods are built by combining different single cell sequencing methods to simultaneously profile multiple types of molecules of a single cell genome wide (Bottom). For example, G&T-seq was built by combining genome (orange) and transcriptome (yellow) to simultaneously detect DNA and RNA of the same cell genome wide.