Cutting of the oligonucleotide by DpnI gives rise to a fluorescence increase. Methyl Sensitive Southern Blotting is similar to the HELP assay, although uses Southern blotting techniques to probe gene-specific differences in methylation using restriction digests. This technique is used to evaluate local methylation near the binding site for the probe. MethylCpG Binding Proteins (MBPs) and fusion proteins containing just the Methyl Binding Domain (MBD) are used to separate native DNA into methylated and unmethylated fractions. The percentage methylation of individual CpG islands can be determined by quantifying the amount of the target in each fraction. Extremely sensitive detection can be achieved in FFPE tissues with abscription-based detection. High Resolution Melt Analysis (HRM or HRMA), is a post-PCR analytical technique. The target DNA is treated with sodium bisulfite, which chemically converts unmethylated cytosines into uracils, while methylated cytosines are preserved. PCR amplification is then carried out with primers designed to amplify both methylated and unmethylated templates. After this amplification, highly methylated DNA sequences contain a higher number of CpG sites compared to unmethylated templates, which results in a different melting temperature that can be used in quantitative methylation detection. Ancient DNA methylation reconstruction, a method to reconstruct high-resolution DNA methylation from ancient DNA samples. The method is based on the natural degradation processes that occur in ancient DNA: with time, methylated cytosines are degraded into thymines, whereas unmethylated cytosines are degraded into uracils. This asymmetry in degradation signals was used to reconstruct the full methylation maps of the Neanderthal and the Denisovan. In September 2019, researchers published a novel method to infer morphological traits from DNA methylation data. The authors were able to show that linking down-regulated genes to phenotypes of monogenic diseases, where one or two copies of a gene are perturbed, allows for ~85% accuracy in reconstructing anatomical traits directly from DNA methylation maps. Methylation Sensitive Single Nucleotide Primer Extension Assay (msSNuPE), which uses internal primers annealing straight 5' of the nucleotide to be detected. Illumina Methylation Assay measures locus-specific DNA methylation using array hybridization. Bisulfite-treated DNA is hybridized to probes on "BeadChips." Single-base base extension with labeled probes is used to determine methylation status of target sites. In 2016, the Infinium MethylationEPIC BeadChip was released, which interrogates over 850,000 methylation sites across the human genome. Using nanopore sequencing, researchers have directly identified DNA and RNA base modifications at nucleotide resolution, including 5mC, 5hmC, 6mA, and BrdU in