PMD hypomethylation human (hg19) neural network scores

<strong>Global loss of DNA methylation in mammalian genomes occurs cumulatively as a mitotic process during aging and cancer, primarily in Partially Methylated Domains (PMDs). It has been shown that local sequence context (100bp) has a strong effect on the rate of demethylation of individual CpG dinucleotides within PMDs. Here, we train a deep learning model to characterize this sequence dependence further, finding that methylation loss can be predicted from a CpG’s 150bp sequence context alone with an AUC of 0.95. We use re-methylation rates of newly synthesized DNA to show that CpGs with fast-loss sequence context are inefficiently re-methylated. Interestingly, we find that the 10% of CpGs predicted to have the “slowest” rate of loss lose almost no DNA methylation in healthy cell types. These same slow-loss CpGs lose a significant amount of DNA methylation in cancer, suggesting that they could be responsible for deregulation of genes and transposable elements that are associated with DNA hypomethylation in cancer.</strong> <strong>This directory contains the Sep. 20, 2020 version of the human (hg19) CpG hypomethylation Neural network scores in one gzip-compressed tsv file per chromosome.</strong> <strong>The Sep. 2020 Neural network score provides a prediction of the probability of each sequence to be a fast hypomethylation CpG, which was produced by a neural network model that used two independent input training datasets.</strong> <strong>Files included in this directory:</strong> <strong> - chr*. tsv.gz: Neural network score of each CpG in each chromosome, using hg19 coordinates. chrX and chrY are omitted.</strong> <strong> <br> Each row is a CG which provides (1) chromosome, (2) the corresponding C coordinate on the forward (watson) strand of the reference genome in one-based coordinates, (3) Neural network score, (4) number of CpGs within the 150bp sequence centered on this CpG, including the center CpG, (5) CpG is within a CpG island (0, no; 1, yes), CpG is within ENCODE blacklist (0, no; 1, yes)</strong> <strong> Here the CpG islands are the union set of Irizarry (Irizarry et al. 2009, Nat Genet), Takai-Jones (Takai et al. 2002, PNAS), Gardner-Gardin CGIs (Gardner-Gardin et al. 1987, J Mol Biol.). The blacklist was downloaded from https://github.com/Boyle-Lab/Blacklist/tree/master/lists.</strong>