TY - JOUR
T1 - Detection and mapping of DNA methylation with 2D material nanopores
AU - Qiu, Hu
AU - Sarathy, Aditya
AU - Schulten, Klaus
AU - Leburton, Jean Pierre
N1 - Funding Information:
This article is dedicated to the memory of Prof. Klaus Schulten, who was one of our closest collaborators and an inspiring colleague for many years. This work was supported by grants from Oxford Nanopore Technology, the Seeding Novel Interdisciplinary Research Program of the Beckman Institute, National Institutes of Health Grant 9P41GM104601 and National Science Foundation Grants PHY0822613 and PHY1430124. The authors gratefully acknowledge also supercomputer time provided through the Extreme Science and Engineering Discovery Environment (XSEDE) Grant MCA93S028 and by the University of Illinois at Urbana-Champaign on the TAUB cluster.
PY - 2017/12/1
Y1 - 2017/12/1
N2 - DNA methylation is an epigenetic modification involving the addition of a methyl group to DNA, which is heavily involved in gene expression and regulation, thereby critical to the progression of diseases such as cancer. In this work we show that detection and localization of DNA methylation can be achieved with nanopore sensors made of two-dimensional materials such as graphene and molybdenum di-sulfide. We label each DNA methylation site with a methyl-CpG binding domain protein (MBD1), and combine molecular dynamics simulations with electronic transport calculations to investigate the translocation of the methylated DNA–MBD1 complex through two-dimensional material nanopores under external voltage biases. The passage of the MBD1-labeled methylation site through the pore is identified by dips in the current blockade induced by the DNA strand, as well as by peaks in the transverse electronic sheet current across the two-dimensional layer. The position of the methylation sites can be clearly recognized by the relative positions of the dips in the recorded ionic current blockade with an estimated error ranging from 0 to 16%. Finally, we define the spatial resolution of the two-dimensional material nanopore device as the minimal distance between two methylation sites identified within a single measurement, which is 15 base pairs by ionic current recognition, but as low as 10 base pairs by transverse electronic conductance detection, indicating better resolution with this latter technique. The present approach opens a new route for precise and efficient profiling of DNA methylation.
AB - DNA methylation is an epigenetic modification involving the addition of a methyl group to DNA, which is heavily involved in gene expression and regulation, thereby critical to the progression of diseases such as cancer. In this work we show that detection and localization of DNA methylation can be achieved with nanopore sensors made of two-dimensional materials such as graphene and molybdenum di-sulfide. We label each DNA methylation site with a methyl-CpG binding domain protein (MBD1), and combine molecular dynamics simulations with electronic transport calculations to investigate the translocation of the methylated DNA–MBD1 complex through two-dimensional material nanopores under external voltage biases. The passage of the MBD1-labeled methylation site through the pore is identified by dips in the current blockade induced by the DNA strand, as well as by peaks in the transverse electronic sheet current across the two-dimensional layer. The position of the methylation sites can be clearly recognized by the relative positions of the dips in the recorded ionic current blockade with an estimated error ranging from 0 to 16%. Finally, we define the spatial resolution of the two-dimensional material nanopore device as the minimal distance between two methylation sites identified within a single measurement, which is 15 base pairs by ionic current recognition, but as low as 10 base pairs by transverse electronic conductance detection, indicating better resolution with this latter technique. The present approach opens a new route for precise and efficient profiling of DNA methylation.
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U2 - 10.1038/s41699-017-0005-7
DO - 10.1038/s41699-017-0005-7
M3 - Article
C2 - 29399640
AN - SCOPUS:85063657806
VL - 1
JO - npj 2D Materials and Applications
JF - npj 2D Materials and Applications
SN - 2397-7132
IS - 1
M1 - 3
ER -