RT Journal Article
SR Electronic
T1 Detecting DNA Methylation using the Oxford Nanopore Technologies MinION sequencer
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 047142
DO 10.1101/047142
A1 Jared T Simpson
A1 Rachael Workman
A1 P. C. Zuzarte
A1 Matei David
A1 L. J. Dursi
A1 Winston Timp
YR 2016
UL http://biorxiv.org/content/early/2016/04/04/047142.abstract
AB Nanopore sequencing instruments measure the change in electric current caused by DNA transiting through the pore. In experimental and prototype nanopore sequencing devices it has been shown that the electrolytic current signals are sensitive to base modifications, such as 5-methylcytosine. Here we quantify the strength of this effect for the Oxford Nanopore Technologies MinION sequencer. Using synthetically methylated DNA we are able to train a hidden Markov model to distinguish 5-methylcytosine from unmethylated cytosine in DNA. We demonstrate by sequencing natural human DNA, without any special library preparation, that global patterns of methylation can be detected from low-coverage sequencing and that the methylation status of CpG islands can be reliably predicted from single MinION reads. Our trained model and prediction software is open source and freely available to the community under the MIT license.