Next-Generation Epigenetic Detection Technique: Identifying Methylated Cytosine Using Graphene Nanopore.
DNA methylation plays a pivotal role in the genetic evolution of both embryonic and adult cells. For adult somatic cells, the location and dynamics of methylation have been very precisely pinned down with the 5-cytosine markers on cytosine-phosphate-guanine (CpG) units. Unusual methylation on CpG islands is identified as one of the prime causes for silencing the tumor suppressant genes. Early detection of methylation changes can diagnose the potentially harmful oncogenic evolution of cells and provide promising guideline for cancer prevention. With this motivation, we propose a cytosine methylation detection technique. Our hypothesis is that electronic signatures of DNA acquired as a molecule translocates through a nanopore would be significantly different for methylated and nonmethylated bases. This difference in electronic fingerprints would allow for reliable real-time differentiation of methylated DNA. We calculate transport currents through a punctured graphene membrane while the cytosine and methylated cytosine translocate through the nanopore. We also calculate the transport properties for uracil and cyanocytosine for comparison. Our calculations of transmission, current, and tunneling conductance show distinct signatures in their spectrum for each molecular type. Thus, in this work, we provide a theoretical analysis that points to a viability of our hypothesis.
Towfiq
T
Ahmed
‡Department of Physics and Astronomy, James Madison University, Harrisonburg, Virginia 22807, United States.
Jason T
JT
Haraldsen
Jian-Xin
JX
Zhu
¶Nordic Institute for Theoretical Physics, KTH Royal Institute of Technology and Stockholm University, Roslagstullsbacken 23, 106 91 Stockholm, Sweden.
Alexander V
AV
Balatsky
DNA methylation; graphene; nanopore; tunneling conductance