Live-cell omics with Raman spectroscopy

Genome-wide profiling of gene expression levels in cells, such as transcriptomics and proteomics, is a powerful experimental approach in modern biology, allowing not only efficient exploration of the genetic elements responsible for biological phenomena of interest, but also characterization of the global constraints behind plastic phenotypic changes of cells that accompany large-scale remodeling of omics profiles. To understand how individual cells change their molecular profiles to achieve specific phenotypic changes in phenomena such as differentiation, cancer metastasis and adaptation, it is crucial to characterize the dynamics of cellular phenotypes and omics profiles simultaneously at the single-cell level. Especially in the last decade, significant technical progress has been made in the in situ identification of omics profiles of cells on the microscope. However, most approaches still remain destructive and cannot unravel the post-measurement dynamics. In recent years, Raman spectroscopy-based methods for omics inference have emerged, allowing the characterization of genome-wide molecular profile dynamics in living cells. In this review, we give a brief overview of the recent development of imaging-based omics profiling methods. We then present the approach to infer omics profiles from single-cell Raman spectra. Since Raman spectra can be obtained from living cells in a non-destructive and non-staining manner, this method may open the door to live-cell omics.