Single-Cell Epigenomics and Proteomics Methods Integrated in Multiomics

The meticulous examination of the genomic, transcriptomic, epigenomic, and proteomic landscapes, conducted at the precise resolution of single cells, has emerged as an indispensable instrument for comprehending the inherent mechanisms governing cellular heterogeneity. These methodologies have provided unprecedented insights into the intrinsic and extrinsic factors that underlie cellular morphological characteristics and differentiated functions. Within this field, multimodal techniques that concurrently analyze the epigenetic features of chromatin or cellular proteins and gene expression within an identical cell delineate intricate gene regulatory networks and phenotypes, thereby enhancing our understanding of cellular states during differentiation or pathological conditions. These techniques can be applied to identify cell subpopulations, infer cell developmental trajectories, and analyze patterns of cell-to-cell communication. In this context, we initiate by delineating the singular cell separation techniques employed in single-cell multiomics. Subsequently, we narrow our focus to methodologies amalgamating epigenetic features with gene expression at single-cell resolution. The epigenetic features entail DNA methylation, chromatin accessibility, histone modifications, chromatin conformation, and transcription factors. Following this, we discuss techniques for the conjoint analysis of cell surface and intracellular proteins in tandem with the transcriptome. Finally, we discuss the challenges and opportunities that manifest within this field, contributing to its continued advancement and exploration.