By Jerry Duggan | Bond LSC
Behind any breakthrough in science lies a research process full of precise methods and instrumentation essential to moving from hypothesis to discovery.
Some of those genetic breakthroughs just became more possible on UM System campuses, thanks to a new, more efficient genome sequencing instrument at MU’s Genomics Technology Core.
The NovaSeq instrument was first put to use in December, purchased with funds from an UM System tier 1 grant meant to benefit all of campus. MU Genomics Technology Core Director Nathan Bivens said this new instrument has significantly increased efficiency of sequencing operations.
“For most projects, we’re able to bring the cost down about 30% compared to our previous instruments,” he said. “This allows us to work more efficiently and increases productivity.”
The sequences behind the problem
According to Wes Warren, primary investigator at Bond LSC, the use of sequencing technology is a crucial need of many scientific investigations. It allows researchers to determine the specific nucleic acid sequence — that is, the order of nucleotide bases-adenine, thymine, cytosine and guanine — in any living thing. The understanding of this sequence variation has already and can in the future lead to real breakthroughs from a human health application standpoint.
“Any novel base change can often be associated with the presence, or absence of a particular trait,” he said.
For example, in many common diseases, such as cardiovascular, variation in the DNA sequence within the individual that has the disease provides clues to the molecular networks associated with its occurrence. This is especially true in polygenic traits — one whose clinical features is influenced by more than one gene, such as cardiovascular disease. According to Warren, sequencing this genetic variation is crucial for understanding these types of traits.
“In order to make sense of many traits and human health conditions, we need to be able to sequence hundreds of thousands of individuals so that we can see and compare that variation,” he said. “Once we have those numbers, we can start to catalog all those sequence changes and assign them some predictive value in the population where we are trying to understand the disease. The importance is in attributing sequence variation toward disease association.”
Investing in the future
Tier 1 grants were rolled out last year as a significant commitment to research, and usually entailed projects or equipment costing in excess of $1 million.
“This instrument is a significant investment on our part, but we expect to get a lot out of that investment over the next several years,” Bivens said. “This instrument is now available for the whole MU system (including the campuses in Columbia, Kansas City, St. Louis and Rolla), so all in the UM system have access to this new infrastructure and will be able to use it.”
Warren is one of those who will benefit from NovaSeq. Warren helped create the proposal that won the grant, and said the instrument itself is but a vehicle to fuel scientific advances in the future.
“Getting this instrument here in a physical sense was big, but an even bigger deal is what we hope it will enable us to do from a research capability standpoint,” he said.
The path to precision medicine
Although sequencing instruments aren’t new to the Genomics Technology Core, our existing instruments were not state of the art for high-throughput genetic studies. High-throughput is the technical term for being able to sequence a large number of samples in a shortened time period. The increased cost efficiency and data precision (higher throughput) comes in handy with the study of cancer cells, because depth of sequencing and larger sample sizes are crucial for discovering mutations. Take, for example, circulating tumor cells in a given individual’s body. The researcher’s goal is to find the cancer cells, of which there are very few, circulating amongst a vast sea of normal cells in the individual’s bloodstream. Use of the NovaSeq instrument will be a key enabler for special strategies to amplify and capture the individual DNA sequences of those hard-to-find circulating cancerous cells.
The potential benefits of sequencing for making human health breakthroughs are boundless, but according to Warren, just as important is what widespread sequencing could mean on an everyday level for patients everywhere.
“A long-term goal is to get to a system where when a patient comes to the doctor there is a blood sample captured and then the genome of the individual is sequenced shortly thereafter” he said. “That individual’s genome would then enter into the electronic health records, and then in the future once we have a population-wide understanding of how sequence variation affects many aspects of human health, physicians will then be able to have access to and utilize all that information.”
While more efficient sequencing has broad, far-reaching benefits, the NovaSeq has already aided specific projects and discoveries on the MU Campus.
One example is Dr. Gary Johnson’s work at the School of Veterinary Medicine, which involves taking whole genome sequences of dogs to look for rare mutations, or changes, in their DNA that can cause a wide range of diseases. Thanks to this new instrumentation, Johnson is able to sequence cheaper and much more quickly. This allows him to get down to the nitty gritty of analyzing DNA sequences for mutations, and in turn, helps identify ways to prevent such diseases that much quicker.
As practical as the new NovaSeq may be, it also represents MU’s symbolic commitment to cutting edge research and scientific discovery.
“This is central to the mission of the DNA core,” said Bivens. “It makes us up-to-date with the most cutting-edge sequencing instruments out there, from a machinery standpoint. More importantly, though, it allows us to offer that technology at a fair cost, which will allow our researchers to be very competitive in terms of writing grants. This instrument is going to set the stage for the next 5 years of research here on this campus very easily, and its benefits are immeasurable to the MU research community.”