The importance of DNA methylation as a key epigenetic regulator of cellular and developmental processes has been widely recognized. Methylation of CpG dinucleotides has been predominantly implicated in transcriptional silencing, particularly when located in promoter regions. More recently, DNA methylation has become a subject of interest due to its role in disease. Many complex diseases show an alteration of DNA methylation that disrupts cellular activity. Take cancer as an example, DNA methylation-mediated transcriptional dysregulation is an early event causing neoplastic transformation, making it an attractive marker for early detection. Methylation signatures differ from one cancer type to another and also from one cell type to another cell type. Understanding the role of these modifications and their effect in different cancer types is crucial to identifying potential targets for treatments and therapies.
To address the gaps in current single-cell DNA methylation methods, a group of investigators from the labs of Renée Beekman and Lars Velten at Centre for Genomic Regulation (CRG), Barcelona, Spain, developed a novel targeted bisulfite-free method. This method, published in Genome Biology and named single-cell targeted analysis of the methylome (scTAM-seq), directly profiles 650 biologically relevant CpG sites in up to 10,000 cells using the Tapestri microfluidic platform.
In this application note, learn how:
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scTAM-seq is a powerful method for investigating DNA methylation dynamics at single-cell and single-nucleotide resolutions
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scTAM-seq enables DNA methylation assessment with high accuracy, achieving a false-positive rate lower than 0.2% combined with a false-negative rate as low as 7%
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scTAM-seq can be combined with somatic mutation and cell surface expression analysis to enable a much richer characterization of tumor heterogeneity
