Protocol for scChaRM-seq: Simultaneous profiling of gene expression, DNA methylation, and chromatin accessibility in single cells

Single-cell multi-omics sequencing technology can infer cell heterogeneity and reveal relationships across molecular layers. Combining single-cell RNA sequencing, DNA methylation, and chromatin accessibility allows a multimodal understanding of cell function and epigenetic regulation within individual cells. Here, we offer a protocol to perform scChaRM-seq (single-cell chromatin accessibility, RNA barcoding, and DNA methylation sequencing), which has been applied to study de novo DNA methylation and its relationship with transcription and chromatin accessibility in single human oocytes. For complete details on the use and execution of this protocol, please refer to Yan et al. (2021).