Single-Cell Multiomics: Multiple Measurements from Single Cells

Abstract

Single-cell sequencing provides information that is not confounded by genotypic or phenotypic heterogeneity of bulk samples. Sequencing of one molecular type (RNA, methylated DNA or open chromatin) in a single cell, furthermore, provides insights into the cell's phenotype and links to its genotype. Nevertheless, only by taking measurements of these phenotypes and genotypes from the same single cells can such inferences be made unambiguously. In this review, we survey the first experimental approaches that assay, in parallel, multiple molecular types from the same single cell, before considering the challenges and opportunities afforded by these and future technologies.

Trends

Unambiguous inference that a cellular phenotype is caused by a genotype can only be achieved by their measurement from the same single cell.

Estimating RNA and DNA copy number abundance in single cells is now possible using a variety of experimental approaches.

Parallel measurement of single-cell epigenomes and transcriptomes provides further insight into the regulation of cellular identity and phenotypes.

Parallel measurement of single-cell transcriptomes and protein abundance (by FACS, proximity ligation assays/PEA or mass cytometry) allows insight into expression dynamics.

Our understanding of cancer progression and diversity is likely to be advanced greatly by the multiomics investigation of single cells, as is our understanding of normal developmental and other disease processes.

Ongoing technological advances will see improvements in the coverage, sensitivity of multiomics approaches, as well the number of analytes that can be surveyed in parallel.