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Big Data's Next Frontier

Big Data's Next Frontier
The Center for Genome Research and Biocomputing.

A decade ago, an international team of researchers with the Human Genome Project sequenced the first human genome. It took them 13 years at a cost of $13 billion. Today, technology borrowed from the Human Genome Project is transforming how we understand our lives and the planet. A new machine can sequence the genetic code of a human cell in mere hours for $1,000.

At Oregon State University, that power lies at its Center for Genome Research and Biocomputing. Almost 100 scientists call this place “the core labs,” where OSU research aims to examine the very building blocks of life.

 

A look at sequencing at the OSU Center for Genome Research and Biocomputing

The technological efficiency of the Center for Genome Research and Biocomputing allows Joseph Spatafora, a professor of botany and plant pathology, to study the molecular world of fungi. These organisms are some of the world’s most effective and yet most enigmatic recyclers.

Spatafora is mapping 1,000 fungal genomes, working with OSU’s center and with the Joint Genome Institute of the U.S. Department of Energy. Spatafora is able to examine large variable data sets cost-effectively. His team’s ultimate aim is ambitious: the development of a fungal genomic reference library to help scientists create new alternative fuels, find organic ways of cleaning up contaminated soils, and improve natural products in food and medicine.

Stephen Atkinson uses the center to map the genetic patterns of a parasite called Ceratomyxa shasta that infects salmon and trout. Understanding those patterns reveals real-time data on parasite densities and their predicted effects on juvenile salmon, explained Atkinson, a postdoctoral scholar in OSU’s Fryer Salmon Disease Laboratory. “By linking areas of high disease risk with physical parameters such as water flows and temperature, hatchery managers can use that information to decide when to release young fish so that they are not exposed to the parasite,” he said.

Soybean leaf in petri dish

This soybean leaf reveals a reporter gene, a type of easily identifiable gene that allows scientists to study the expression of a nearby gene or sequence. (Photo by Lynn Ketchum.)

Brett Tyler directs the center and its cornucopia of vast sequencing machines, genotyping computers, and sophisticated microscopes. Its machines can sequence DNA, a molecule that serves as a cell’s “instruction manual” for making protein; and RNA, chains of cells that make the protein.

The center’s server room feeds that infrastructure with enough electricity to power 100 houses. Think of those servers as “Google meets biology.” Inside those servers, elaborate software analyzes huge amounts of data. The sheer quantity of data has increased as technology has become cheaper.

“The center can provide a high level of expertise in analyzing genome sequencing data,” said Tyler. “Its ability to generate new genome sequence data and analyze those data is unavailable to an individual lab because of the expense.”

Tyler leads his own research team and studies oomycetes, a class of tiny kelp-like organisms that includes notorious pathogens of many important crops. “Most of our work is focused on how plant pathogens work against plants to affect their immune systems, just as doctors try to understand how microbes are successful at breaking down human immune systems,” Tyler said.

preparing DNA for sequencing

Scientists prepare DNA from hop plants for sequencing. The result can pinpoint variation in a DNA sequence that will allow plant breeders to more precisely find traits such as flavor or cold hardiness in a genome. (Photo by Lynn Ketchum.)

This technology has worldwide impact. In Asia, hurricanes can force floods of salt-tainted seawater into rice paddies and upset livelihoods. Pankaj Jaiswal, a plant biologist, studies traits such as salt tolerance within the rice genome. Jaiswal is comparing varying levels of salt tolerance in various rice varieties by exploring how the expression of genes is regulated under high salt versus normal conditions. By identifying genes responding to high salt conditions, the research will help plant breeders use these genes for developing salt-tolerant varieties.

Jaiswal’s methods support classical plant breeding techniques. “We can improve varieties with beneficial traits such as high yield and salt and drought tolerance through conventional breeding, and identify candidate genes with genomic mapping,” Jaiswal said.

And, center director Tyler collaborates with researchers in China to analyze large amounts of biological data, which has earned him China’s highest prize for non-Chinese scientists.

Siva Kumar

Siva Kumar Kolluri, an OSU cancer researcher, uses 96-well plates to rapidly screen chemical compounds in order to identify potential cancer therapeutics. (Photo by Lynn Ketchum.)

Finally, cracking the genetic code can yield insights into one of humanity’s most baffling enigmas—cancer. Siva Kolluri, an OSU cancer researcher, uses the center’s fast, automated analyses to gain new insight into the inner workings of cancer cells.

His research team investigates new cancer drugs that can target and kill abnormal cells. Kolluri investigates how certain proteins known as “nuclear receptors” regulate gene expression upon interacting with chemical compounds. If he can find the right key with which to unlock certain members of this protein family, Kolluri can direct them to suppress growth of abnormal cells.

His laboratory screens thousands of chemical compounds to identify new anti-cancer compounds that selectively eliminate abnormal cells. The idea behind all these tests is to find the most effective compounds that will transform certain proteins into cancer-fighting proteins.

“This cutting-edge technology is almost impossible for an individual lab to acquire on its own, but it is now essential to answer our research questions,” Kolluri said. “When I’m competing for new research funding, an important component of my proposal has to be innovation. I need to show that I’m going beyond known techniques and using new technology to answer novel research questions,” he said. “For that kind of innovation, this facility is a must.”

In the vanguard of vegetable breeding

Jim Meyers

OSU vegetable breeder Jim Myers evaluates the results of years of plant breeding. (Photo by Lynn Ketchum.)

Oregon State University began its vegetable-breeding program in 1951, just a few years before James Watson and Francis Crick determined that DNA was shaped like a double helix.

Today, OSU vegetable breeder Jim Myers develops better vegetables using genomic tools that have evolved from that historic discovery. Although classical plant breeding techniques remain at the heart of his efforts, Myers uses molecular-level analyses to more precisely find traits (such as disease resistance) within large, complex plant genomes and to determine how those genes function and express themselves.

This is not genetic engineering, but rather traditional plant breeding using information accessible through OSU’s Center for Genome Research and Biocomputing. Myers makes crosses among selected vegetables by analyzing the observable physical parts, or the phenotype, of the plants in field trials. He looks at fragments of DNA that will tell him more about the location of certain traits in a gene. And he discovers how each gene creates proteins.

“Low-tech breeding requires that you spend a lot of time out in the fields testing environmental influences,” Myers said. “The volume of molecular data that you can access through the center helps to sift through a lot of junk DNA. It lets you focus on the material you really need and work more efficiently with traits that are difficult and time-consuming to evaluate in the field before you conduct trials.”

All the molecular shortcuts at Myers’ disposal may sound futuristic, but they are simply the next level of conventional plant breeding. Marker-assisted selection, which is a method of selecting individuals to breed based on their molecular patterns, “gives you better underlying knowledge of how traits are controlled by a gene,” Myers said. Currently, he is using genomic tools to develop green bean varieties that are resistant to white mold. He’s also developing new broccoli varieties for vegetable processors, a disease-resistant “Golden Delicious” pumpkin, and improved stringless snap peas, all practical applications of an elegant double helix.

Published in: Innovations