Detection of cancer biomarkers from blood samples

Pattern recognition of miRNA expression using DNA computing and nanopore decoding

Image: Pattern recognition of miRNA expression using DNA computing and nanopore decoding
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Credit: Ryuji Kawano, Tokyo University of Agriculture and Technology

Cholangiocarcinoma, also known as bile duct cancer, is a cancer type with a characteristically high mortality. At the time of diagnosis, most bile duct cancers are usually incurable. This is why methods of early diagnosis of bile duct cancer are urgently needed.

Liquid biopsy, the sampling of non-solid biological tissue such as blood, is gaining interest as a rapid and non-invasive method of diagnosing cancers. Unlike traditional biopsies that require surgery and often general anesthesia, a liquid blood biopsy requires only a few milliliters of blood, with minimal harm to the patient.

After sampling, the blood is screened for specific markers that indicate the presence of cancerous tissue. For example, specific patterns of microRNA (miRNA), short non-coding strands of RNA, are associated with different cancers and can be used to diagnose cancers from liquid biopsies with high precision. However, the low concentration of miRNA in the blood samples makes their detection challenging.

Researchers from Tokyo University of Agriculture and Technology have developed a new method for the detection of cancer miRNA patterns based on DNA computer technology. The developed method shows potential as a promising tool for simple and early cancer diagnosis from liquid biopsies with low concentrations of target biomarkers. The findings are published in the peer-reviewed journal JACS Au on June 26, 2022.

“DNA computing uses the biochemical reactions of the information-encoding DNA molecules to solve problems based on formal logic, in the same way that normal computers do,” said corresponding author Ryuji Kawano, a professor at the Tokyo University of Agriculture and Technology (TUAT) in Japan. “In this case, a diagnostic DNA molecule was designed to be able to bind five different types of miRNA associated with bile duct cancer. While binding the miRNA molecules, the diagnostic DNA converts the expression pattern of the miRNAs into the information in the form of a nucleic acid structure.”

To read this information, the scientists use a method called nanopore decoding. In this method, the DNA is passed through a nano-sized hole or “pore”. If the molecule passes through the pore, it will impede the flow of electrical current through the pore. These perturbations in the flow through the pore can then be measured and used to infer the properties of the passing molecule. In the case of the diagnostic DNA, the bound miRNAs will be “unpacked” from the DNA, resulting in a current inhibition of characteristic amplitude and duration. By statistically analyzing the extract data from the miRNA patterns, the scientists were able to recognize cancer-specific expression patterns even from clinical samples with extremely low concentrations of miRNA. This is a significant improvement in nanopore diagnosis, as nanopore measurements have generally been considered unable to detect nucleic acids at such low levels, undermining the use of the technology in clinical applications.

For more information about the Kawano laboratory, please visit: http://web.tuat.ac.jp/~rjkawano/index_en.html

Original publication:

Nanami Takeuchi, Moe Hiratani and Ryuji Kawano*,
Pattern recognition of microRNA expression in body fluids using nanopore decoding at sub-femtomolar concentration
JACS Au2022,
https://doi.org/10.1021/jacsau.2c00117
*: Corresponding Author

About Tokyo University of Agriculture and Technology (TUAT):

TUAT is a leading university in Japan dedicated to science and technology. TUAT focuses on agriculture and engineering that are the foundation of industry, and promotes areas of education and research that incorporate them. With a history spanning more than 140 years since our founding in 1874, TUAT continues to boldly take on new challenges and steadily promote fields. With high ethics, TUAT fulfills social responsibility in the capacity of transferring scientific and technological information to the construction of a sustainable society in which both humans and nature can thrive in a symbiotic relationship. For more information, visit http://www.tuat.ac.jp/en/


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