November 21, 2019

Researchers teach hand-held DNA sequencing devices to read a new language

Paul Tang, Computational Biologist, and Philip Zuzarte, Scientific Associate pose for a photo at OICR headquarters.
Paul Tang, Computational Biologist, and Dr. Philip Zuzarte, Scientific Associate pose for a photo at OICR headquarters. Tang and Zuzarte were central to OICR’s contributions to the study.

International research group unlocks the promise of nanopore native RNA sequencing

Studying RNA may offer new answers to cancer – and the tools to read RNA directly are now in our hands.

An international research consortium, led in part by Dr. Jared Simpson at OICR, has developed new laboratory protocols and a suite of software tools that will allow the research community to exploit the promise of direct RNA sequencing.

Dr. Jared Simpson, OICR Investigator.

These techniques, published recently in Nature Methods, represent the first large-scale exploration of human RNA using nanopore sequencers – the advanced handheld sequencing devices that can read long strands of RNA.

“Unlike traditional sequencing devices that read copies of RNA strands that are cut into little pieces, nanopore sequencing allows us to study long strands of RNA directly without losing important information in the copying and cutting process,” says Paul Tang, Computational Biologist at OICR and co-first author of the publication. “Our methods combine the power of reading RNA directly with the power of long-read sequencing, enabling an entirely novel way to study cancer biology.”

In collaboration with researchers at Johns Hopkins University and the University of California Santa Cruz, Tang and Simpson developed the software methods that could decode the output data from a nanopore sequencer. Their methods used a machine learning technique, called a Hidden Markov Model, to determine the letters of code within an RNA strand.

“With these methods, we’ve shown that you can leverage nanopore RNA sequencing to gain a lot of valuable information that we couldn’t have otherwise,” Tang says. “We’re very happy to see this work published because we are enabling others to study a new aspect of cancer biology and we look forward to the research discoveries to come.”

These new methods have been integrated into Simpson’s already-popular nanopolish software suite which is routinely used by the nanopore community around the world.

Read more about Simpson’s work in our 2018-2019 Annual Report.

February 23, 2017

New Gene Sequencing Software Could Aid in Early Detection, Treatment of Cancer

A closeup of the nanopore sequencing device

Digital Detection Tool Will Be Shared Freely Over the Web

Toronto, ON and Baltimore, MD (February 23, 2017) A research team from the United States and Canada has developed and successfully tested new computational software that determines whether a human DNA sample includes an epigenetic add-on linked to cancer and other adverse health conditions.

Continue reading – New Gene Sequencing Software Could Aid in Early Detection, Treatment of Cancer

June 16, 2016

OICR-developed software helping track Zika in Brazil

Field Laboratory tracking Zika
Photo: University of Birmingham

Scientists from the University of Birmingham in the U.K. have established a mobile DNA sequencing lab in Brazil to help that country track the spread of the Zika virus. The lab, based inside a minibus, is travelling through the areas of Brazil that have been most affected. A central part of the technology they are using is the small, USB-powered MinION genome sequencer. OICR’s Dr. Jared Simpson, an Investigator in the Informatics and Bio-computing Program, developed the software used to sequence samples on the device.

Read the news release: Mobile laboratories help track Zika spread across Brazil

Related: Tracking Ebola with portable sequencers: Could this technology be the key monitoring the spread of Zika?

May 3, 2016

Tracking Ebola with portable sequencers

Could this technology be the key to monitoring the spread of Zika?

Jared Simpson with MinION sequencer

As West Africa was dealing with a massive outbreak of the Ebola virus, a group of researchers answered the call for assistance with a palm-sized device. Dr. Nick Loman and Mr. Josh Quick from the Institute of Microbiology and Infection at the University of Birmingham in the U.K., together with the help of OICR Investigator Dr. Jared Simpson, developed a ‘genome sequencing lab in a suitcase’ based around the tiny MinION sequencer. It was deployed to Conakry, Guinea in April of 2015 to test Ebola samples in the field.

Continue reading – Tracking Ebola with portable sequencers

June 15, 2015

Researchers sequence and assemble first full genome of a living organism using technology the size of smartphone

TORONTO, ON (June 15, 2015) Researchers in Canada and the U.K. have for the first time sequenced and assembled de novo the full genome of a living organism, the bacteria Escherichia Coli, using Oxford Nanopore’s MinIONTM device, a genome sequencer that can fit in the palm of your hand.

The findings, which were published today in the journal Nature Methods, provide proof of concept for the technology and the methods lay the groundwork for using it to sequence genomes in increasingly more complex organisms, eventually including humans, said Dr. Jared Simpson, Principal Investigator at the Ontario Institute for Cancer Research and a lead author on the study.

“The amazing thing about this device is that it is many times smaller than a normal sequencer – you just attach it to a laptop using a USB cable,” said Simpson. “And while our work is a demonstration of the capabilities of the technology, the most significant advance is in the methods. We were able to mathematically model nanopore sequencing and develop ways to reconstruct complete genomes off this tiny sequencer.”

While standard sequencing platforms can either generate vast amounts of data, or read long enough stretches of the genome to allow complete reconstruction, the Nanopore device has the potential to achieve both goals according to Simpson. “Long reads are necessary to assemble the most repetitive parts of genomes but we need a lot of reads if we want to sequence human genomes. The small size of the MinION suggests there is room to scale up and sequence larger and more complex samples,” Simpson said.

A drawback of the technology is that the single reads it produces are currently much less accurate than the reads produced by larger devices. Strong bioinformatics tools are needed to correct errors. The methods Simpson and colleagues developed are able to overcome the error rate and compute a more accurate final sequence.

“This was a fantastic example of a successful long distance research collaboration between Canada and the U.K.,” said Dr. Nicholas Loman, a co-lead author on the paper and an Independent Research Fellow from the Institute of Microbiology and Infection at University of Birmingham. “We explored new ways of working, including hosting a hackathon to explore new algorithm development and using shared computing resources on the Medical Research Council funded Cloud Infrastructure for Microbial Bioinformatics (CLIMB) based in the U.K. Midlands and Wales.”

The method of assembly the authors devised had three stages. First, overlaps between sequence reads are detected and corrected using a multiple alignment process. Then the corrected reads are assembled using the Celera assembler and finally the assembly is refined using a probabilistic model of the electric signals caused by DNA moving through the nanopore.

“This work has incredible potential,” said Dr. Tom Hudson, President and Scientific Director of the Ontario Institute for Cancer Research. “Scaled up, this technology could one day be used to sequence tumour genomes. The device’s portable nature would allow for sequencing to become far more accessible, bringing the option of more personalized diagnosis and treatment to more patients.”