Identification of epigenetic DNA modification in cancer tissues from raw next generation sequencing dataстатья

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[1] Identification of epigenetic dna modification in cancer tissues from raw next generation sequencing data / L. A. Uroshlev, E. T. Abdullaev, I. R. Umarova et al. // Scentific Reports (Nature). Abstract In the course of sample preparation for some methods of Next Generation Sequencing (NGS) DNA is fragmented by various methods. However, the fragmentation shows a persistent bias with regard to the cleavage rages of various dinucleotides. With the exception of methylated CpG dinucleotides the previously described biases were consistent with previous results of the DNA cleavage in solution. Here we computed cleavage rates of all canonical dinucleotides including the methylated CpG and unmethylated CpG dinucleotides using data from the Whole Genome Sequencing datasets of the 1000 Genomes project. We found that the cleavage rate of CpG is significantly higher for the methylated CpG dinucleotides. Using this information, we developed a classifier for distinguishing cancer and healthy tissues based on their status of the CpG island segmentation. A simple Support Vector Machine classifier based on this algorithm shows an accuracy of 84%. The proposed method allows the detection of epigenetic markers purely based on mechanochemical DNA segmentation, which can be detected by a simple analysis of NGS sequencing data.

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