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Publications of the Week

Increasing the Accuracy of Nanopore DNA Sequencing Using a Time-Varying Cross Membrane Voltage

By May 8, 2019No Comments

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This week we profile a recent publication in Nature Biotechnology from Dr. Matt Noakes
(third from left, back row) and Dr. Jens Gundlach at the University of Washington.

Brief overview of lab’s current research focus:

Our lab has been instrumental in developing “nanopore sequencing”, a technology that can electronically read the sequence of DNA molecules. Nanopore sequencing has several advantages over existing DNA sequencing methods. Nanopore sequencing can directly read long pieces of DNA, while conventional methods must piece the DNA’s sequence together from short fragments of DNA. Nanopore’s long reads enable scientists to understand parts of the genome that cannot be read using other methods. Additionally, nanopore sequencing has the potential to be faster, cheaper, and more portable than other technologies, making it an attractive option both in the clinic and in the field. However, nanopore sequencing is still a relatively new technology and has a few limitations, most notably its relatively high error rate i.e. the percentage of incorrectly identified DNA bases.

What is the significance of the findings in this publication:

The high error rate limits the impact of nanopore sequencing in applications where high accuracy is important. In these cases, a researcher or clinician must either collect many low accuracy reads of the same DNA to average over the errors (increasing the time and cost) or use another higher accuracy method in conjunction with the nanopore sequencer to check for errors.

In this publication, we demonstrate a modification to the nanopore sequencing technique that reduces the error rate by a factor of 2. To accomplish this, we identified two of the primary sources of error in the system. We then made a simple change to the operation of the nanopore sequencer which mitigates both error sources. The higher accuracy reads enabled by this advance will make nanopore sequencing useful to a broader range of DNA sequencing problems and further reduce the time and cost of nanopore sequencing.

What are the next steps for this research:

The error rate reduction reported in this work is an initial proof-of-concept showing the potential of our modified nanopore sequencing method, but is not a final bound on what is possible using this method. Our lab is continuing to improve and refine this method to further reduce the error rate. This will entail the collection of large data sets using the modified nanopore sequencing technique, and the development and training of better algorithms to extract the DNA sequence data from our measured signals.

In addition to further in-house improvements, we hope to see this method adapted into commercial nanopore sequencing devices. The new method proposed by this publication requires only a minor re-engineering of existing nanopore sequencing devices, accompanied by new software, to take advantage of a big improvement in error rate. We are optimistic both about the ease of implementation and the magnitude of the resulting effect.

This research was funded by:

We research is funded by the National Institutes of Health, National Human Genome Research Institute (NHGRI), grant number R01HG005115.

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