New technology at Wash U maps human genome in days; large-scale studies now possible
New technology at Wash U maps human genome in days;
large-scale studies now possible
April 25, 2015 11:15 pm
• By Michele Munz
The two 3-inch-by-1-inch glass chips held the
unfathomable amount of genetic information contained in 16 human genomes. On
Thursday, a technician placed the chips — called flow cells — in a new genetic
sequencing machine at the Genome Institute at Washington University and closed
the door.
In just three days, the task will be complete.
It’s mind-boggling given that it took scientists working
all over the world more than 10 years and about $1 billion to first sequence
the human genome, a feat declared officially complete in 2003.
This ultra-fast sequencing machine, which hit the market
last year, is only sold in groups of 10 — a system capable of sequencing 18,000
human genomes a year at just $1,000 to $1,500 per genome.
Washington University’s Genome Institute will receive its
10th HiSeq X machine by the end of this month, each one costing $1 million.
The massive increase in speed and drop in the cost of
sequencing allows scientists to take on studies of unprecedented scale, which
is necessary to make the conclusions and discoveries about human disease that
doctors can put into everyday practice with personalized treatments.
“We have an opportunity to push genomics into the clinic
and understand what causes disease and ultimately learn how to predict
disease,” said Rick Wilson, director of the Genome Institute.
That was the goal and hope when laboratories like the
Genome Institute joined together in the early ’90s to tackle the seemingly
impossible task of mapping the human genome.
“It’s like being right at the beginning,” Wilson said.
“It’s like a rocket ship, really. This rocket ship will take us places the old
rocket ship couldn’t.”
When the technology was first announced last year,
quantitative biologist Michael Schatz of Cold Spring Harbor Laboratory in New
York likened it to the development of the telescope or the microprocessor,
which made the modern personal computer possible.
Schatz told the scientific journal Nature: “If there was
any doubt that genomics would ever be able to reach the everyday man, at this
price point and efficiencies, it is absolute certainty.”
TENS OF THOUSANDS
What in our genes causes us to have arthritis, diabetes
or a cancer that doesn’t respond to treatment? To uncover the answers in the 6
billion bases of DNA that make up the human genome requires sequencing
populations.
“If you have 10,000 people with Alzheimer’s and 10,000
people who never showed signs of the disease, the idea is that you could
sequence both those groups and learn something about Alzheimer’s,” Wilson
explained. “Because every human is different from every other human, you can’t
do that with just five people with Alzheimer’s and five people without. You
won’t have enough data to pinpoint the differences.”
That is the reason the new sequencers are sold in groups
of 10, according to their maker, San Diego-based Illumina.
“These systems support large-scale human whole-genome
sequencing projects,” said Illumina senior market manager Joel Fellis. “The
goal is to deliver both a compelling price and the sequencing capacity needed
to sequence thousands to tens of thousands of samples.”
The $10 million price also ensures that only institutions
equipped with the expertise to decipher and store the data are sitting at the
high-stakes poker table of genomics. The Genome Institute is one of seven
laboratories in the U.S. that have the HiSeq X Ten, and one of 20 worldwide.
“I felt that if we didn’t buy into the state-of-the-art
technology, there was a possibility we would be left behind,” Wilson said. “I
thought it was important to the region to continue to have one of the best
places in the world to study modern genomics.”
The Genome Institute was a key player in the Human Genome
Project, ultimately contributing 25 percent of the blueprint, thanks partly to
quadrupling the speed of sequencing by developing a way to identify the four
bases that make up DNA with fluorescent dye and lasers. In 2008, the institute
was the first to sequence the cancer genome of a leukemia patient and has since
sequenced 750 pediatric cancer patients, leading to discoveries in 22 types of
cancer.
“The Genome Institute has been a pioneer of both Illumina
technology and human whole-genome sequencing, particularly in the study of
cancer genomics,” Fellis said. “Many of the world’s first cancer genomes were
sequenced in St. Louis, and we are excited to see how they use this technology
on a massive scale.”
While the institute has learned a lot by sequencing a
person’s cancer cells and normal cells and comparing the two, Wilson said he is
seeking federal grants to use the new sequencing technology to uncover genetic
clues about more complex diseases such as heart disease, diabetes and
autoimmune disorders.
‘NOTHING FLASHY’
Twenty-five years ago, scientists dispensed solutions
into a large test tube where they prepared DNA to be sequenced. The process evolved
from smaller test tubes to a tray of 96 centimeter-size wells filled by robots.
The number of wells further increased to 384. Next came millions of tiny divots
on a plate.
The flow cell contains a lawn-like surface that can hold
about 3 billion DNA molecules that can all be sequenced at the same time —
which scientists call “massively parallel.”
“The chip is like thousands and thousands of lab
technicians sitting at a lab bench,” Wilson said. “There’s a whole bunch of
stuff happening at the same time.”
Rooms of equipment and lab technicians at the Genome
Institute have been replaced by rooms of researchers sitting at computers. Bob
Fulton, director of project management, said he never imagined he would be
spending much of his day in front of a screen, looking at machine matrix data
and quality measurements.
“I don’t even know where my lab coat is,” he said,
laughing. “Tours of this place used to be so cool with robots moving and
lifting and squirting things. Now it’s boring. It’s nothing flashy.”
The massive breakthroughs on the sequencing side have
required equal advancements in the ability to store and analyze the information
output. One human genome alone contains enough data to fill a phone book the
size of the Washington Monument.
Across the street from the Genome Institute is a
12,000-square-foot data center housing supercomputers and servers with its own
cooling plant and electrical substations. The equipment is constantly being
upgraded with the latest technology, Wilson said, and software engineers are
always working to develop new ways to compress the data, make faster
comparisons and quickly delete what is not needed.
Given the breakneck speed of advancements in genomics
over the past 20 years, the trajectory is hard to imagine.
“In five years,” Wilson said. “My iPhone or something
like it is going to sequence my genome.”
Comments
Post a Comment