Genome-wide bulk sequencing is widely used to assess DNA methylation (DNAm). However, methylation signals obtained from bulk sequencing are averaged out, concealing the cell-to-cell differences in methylation signatures involved in health and disease. Single-cell methods such as bisulfite sequencing were developed to reveal these signatures and offer insights into cellular heterogeneity and rare cell types. However, genome-wide DNAm profiling at single-cell resolution has drawbacks such as sparse data and limited genomic coverage even for deeply sequenced samples.

To address this gap, the Renée Beekman Lab and the Lars Velten Lab of the Centre for Genomic Regulation (CRG) in Barcelona teamed up to develop a novel high-throughput, high-confidence targeted bisulfite-free method for analyzing DNAm in single cells, now published in Genome Biology.

In this webinar, authors Michael Scherer, Ph.D. and Agostina Bianchi of CRG will present the Single-Cell Targeted Analysis of the Methylome (scTAM-seq) protocol which profiles 650 biologically relevant CpGs in up to 10,000 cells using the Tapestri platform. They will also share how they combined DNAm (epigenetics), somatic mutations (genotype), and surface marker expression (phenotype) to gain a rich picture of clonal architecture and dynamics across B cell differentiation in blood and bone marrow.