New Genome Sequencing Instrument Pays Dividends at DNA Core

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 DNA 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 DNA 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 DNA 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.”

Article originally published on Decoding Science.