By Heather Hamilton, contributing writer
In 2012, Oxford Nanopore unveiled a sequencing USB device no larger than a typical USB drive, smaller than a deck of cards. Though innovative, it was problematic — some delays and a host of inaccuracies. By taking single strands of the double helix and putting them through a protein pore, the sequencer sent a small amount of current through the pore. Ars Technica reports that the four bases of DNA each created a change in voltage that was used to read DNA individually.
Six years later, researchers have found new use in the nanopore by focusing on what it does well. In a paper published in Nature Biotechnology , the researchers describe how the long reads provided by the sequencer allow for sequencing of the human genome in areas that formerly resisted characterization. The device could also determine two sets of chromosomes from the other and locate areas of epigenetic control across the genome.
The sequencer was developed by Professor Nick Loman at the Institute of Microbiology and Infection at the University of Birmingham and Ph.D. student Josh Quick. Quick played a large role in developing the long read method.
While the device is still prone to errors, it excels where sequencers with higher accuracy fail, which is when they’re asked to read DNA in chunks of higher than 200 bases. When DNA is repetitive, other software programs struggle. Together, highly accurate devices and Oxford Nanopore’s smaller device offer a compromise, providing sequences and then demonstrating how sequences form bigger portions.
The research explores ways to generate the best sequence possible of nanopores via different software solutions and interpretations of voltage data. By performing multiple reads and drawing on a number of methods, researchers reached an accuracy of 99.44%.
Ars Technica explains that, because we inherit two copies of each chromosome — one from each parent — the underlying DNA is identical for long stretches, even though the copies are different. This means that short DNA reads cannot determine which is which. In this case, the long read provided by the nanopore is essential. During their experiments, researchers found that they could read lengths as high as 882,000 bases, which couldn’t be done in the initial project to sequence the human genome. They predict that this new application could help fill all of the gaps in the original genome project.
The researchers did run into some trouble when they discovered that the common file format used to hold DNA data was unequipped to handle overly long sequences, causing the analysis software to malfunction. Of course, if the software can be updated to include this capability, the possibilities are endless.
“Until even just a year ago, it would have been impractically difficult to sequence a whole human genome, but thanks to recent advances and innovations such as nanopore technology, we now have the ability to sequence very long fragments of the genome,” says Loman in a press release from the University of Birmingham. He likens it to a jigsaw puzzle.
“One of the most important findings of this research was that, even though the human genome reference was completed or thought to have been completed a while ago, it still contains many missing pieces, and we were able to close some of those gaps in the sequence by developing a new method for developing these extremely long reads using nanopore sequencing,” he says.
Sources: Ars Technica, Nature Biotechnology, University of Birmingham
Image Source: Pixabay
Advertisement
Learn more about Electronic Products Magazine
