DNA tasting makes real-time selective sequencing a reality

A NOVEL pocket-sized DNA sequencer of the type used on the International Space Station can also be used to preselect DNA strands for sequencing – greatly reducing biological sample analysis time.

FAST AND LOOSE: Matt Loose demonstrates the fast new ‘Read Until’ DNA sequencing method with the Minion sequencer at the University of Nottingham

Researchers at the University of Nottingham UK, developed the new method of selective sequencing using a Minion portable DNA sequencer from Oxford Nanopore Technologies.

The technique, called ‘read until’, allows the user to determine which DNA strands are to be analysed based on the presence of a signature of interest.

These signatures are based on tiny fluctuations in a current trace (called squiggles) produced in the nanometre-sized pores in the Minion device.

Minion can sense the sequence of DNA fragments passing through tiny molecular pores, producing very small fluctuations in a current trace.

The traces or squiggles have previously been compared to datasets in the cloud, in order to be converted to DNA bases.

This slowed the process and meant that real-time analysis was not possible.

The Nottingham team, led by Dr Matt Loose, bypassed this step by using signal processing to map the onto reference sequences.

They showed that this can be performed fast enough to enable decisions about the fragment of DNA being sequenced to be made even before it has passed through the nanopore.

This means that individual nanopores within the device can be instructed to continue sequencing or to eject the current fragment and start on the next.

This real-time selective sequencing, or ‘DNA tasting’, can reduce the time to sequence key DNA fragments or enable the analysis of pathogen samples where there is host and other DNA present in the sample, they conclude.

Describing the work in the journal Nature Methods today (25 July 2016), Dr Loose says this is the first time any device has demonstrated the direct selection of specific DNA molecules.

“This makes sequencing as efficient as possible and will provide a viable, informatics based alternative to traditional wet lab enrichment techniques” he said.

“We hope that it will enable many future novel applications, especially for portable sequencing.”

A Minion has recently been sent to the International Space Station to investigate whether DNA sequencing is possible in microgravity.

Leave a Reply

Your email address will not be published. Required fields are marked *