Tyler O'Neal, Staff Editor ACADEMIA

Montana State computer scientists help expand horizon of genetics research

A tweaked gene or two among the millions or even billions of proteins that make up an organism's DNA are often all that distinguish the drought-tolerant plant or the person pre-disposed to cancer.

That's why a better understanding of genetic variation within a species could, among other things, help improve the selection of crops for local conditions and detection of disease, according to Joann Mudge, a senior research scientist at the nonprofit National Center for Genome Resources.

A generation ago, recording an organism's DNA from beginning to end was so laborious and expensive that scientists celebrated when they completed the task for a single bacterium. But as genome sequencing becomes faster and cheaper, scientists increasingly have access to insights about which genes do what, Mudge said.

"We're sequencing multiple individuals of some species," including plants and other complex organisms, Mudge said. That allows scientists to begin to sort out which segments of DNA from a species' core genome and which correspond to traits shared by only some individuals, she said. CAPTION Montana State computer science professor Brendan Mumey, right, and assistant professor Indika Kahanda, guide graduate students Lucia Williams and Buwani Manuweera through coding as part of the pangenomics project on May 16, 2019. CREDIT MSU Photo by Adrian Sanchez-Gonzalez{module In-article}

But the growing field of pangenomics, as it is called, presents a major analytical challenge. That's why NCGR recently partnered with Montana State University computer scientists to develop software that can compare multiple genomes and make sense of the results. The project is backed by a three-year, $662,000 grant from the National Science Foundation.

"We've been very happy with the way it's working," said Brendan Mumey, a professor in the Gianforte School of Computing in MSU's Norm Asbjornson College of Engineering. He and Mudge are co-leading the project.

According to Mumey, previously available software struggled with analyzing pangenomes for relatively primitive organisms such as the common yeast Saccharomyces cerevisiae, whose genome contains only 12 million of the DNA units known as base pairs. (By comparison, the human genome contains 3 billion base pairs.) Among the known strains of the yeast, minor genetic variations account for physical adaptations such as the ability of brewer's yeast to survive alcohol during the making of beer and wine.

"It's a classic 'big data' problem," Mumey said, referring to the field of supercomputing that deals with exceptionally large and complex data sets.

MSU assistant professor of computer science Indika Kahanda, a member of the research team, specializes in developing the "machine learning" models that help the new software adjust its gene-sorting analysis according to input from scientists. That approach has helped the team, which includes NCGR research scientist Thiru Ramaraj, identify genes of interest in a yeast pangenome that includes roughly 100 strains. Ramaraj earned his doctorate in computer science in 2010 at MSU, where Mumey was his adviser.

Mumey said the researchers' next step is to continue to refine the software so it can handle larger and more complex genomes, such as those of plants. The computational techniques being used "are still in their infancy," he said.

Eventually, pangenomics could help medical professionals diagnose a variety of diseases that have a genetic component, Mudge said. Most inherited breast cancer can be traced to mutations in just two genes, but other genetic diseases are thought to stem from more complex changes across larger areas of DNA.

The improved pangenomics tool is already helping scientists break out of a mold of comparing genomes to a single, arbitrary reference, Mudge said. Instead, researchers can represent a species' entire genome with all its nuance and variety.

"It's a hard problem to solve," Mudge said. "This has been a great collaboration."

University of Tokyo researcher tracks extinct species on ancient Earth via biogeography

Tyler O'Neal, Staff Editor ACADEMIA

One researcher at the University of Tokyo is in hot pursuit of dinosaurs, tracking extinct species around ancient Earth. Identifying the movements of extinct species from millions of years ago can provide insights into ancient migration routes, interaction between species, and the movement of continents.

“If we find fossils on different continents from closely related species, then we can guess that at some point there must have been a connection between those continents,” said Tai Kubo, Ph.D., a postdoctoral researcher affiliated with the University Museum at the University of Tokyo.

A map of life — biogeography
Previous studies in biogeography — the geographic distribution of plants and animals — had not considered the evolutionary relationships between ancient species. The new method that Kubo designed, called biogeographical network analysis, converts evolutionary relationships into geographical relationships. How to track a dinosaur. By combining data from fossils and models of the ancient Earth, researchers can map where ancient species may have migrated. This method, called biogeographical network analysis, converts evolutionary relationships between species into geographical relationships. This method was used in research by Tai Kubo, Ph.D., a postdoctoral researcher affiliated with the University Museum at the University of Tokyo. Image by Caitlin Devor, The University of Tokyo{module In-article}

For example, cats and dogs are more closely related to each other than to kangaroos. Therefore, a geographical barrier must have separated the ancestors of kangaroos from the ancestors of cats and dogs well before cats and dogs became separate species.

Most fossils are found in just a few hot-spot locations around the world and many ancient species with backbones (vertebrates) are known from just one fossil of that species. These limitations mean that a species' fossils cannot reveal the full area of where it was distributed around the world.

"Including evolutionary relationships allows us to make higher resolution maps for where species may have migrated,” said Kubo.

The analysis used details from evolutionary studies, the location of fossil dig sites, and the age of the fossils. Supercomputer simulations calculated the most likely scenarios for the migration of species between continents on the Cretaceous-era Earth, 145 to 66 million years ago.
Early Cretaceous biogeographical map of nonavian dinosaurs. During the Early Cretaceous period (145-100 million years ago), nonavian dinosaurs likely migrated between Africa and Europe. The results are part of research by Tai Kubo, Ph.D., a postdoctoral researcher affiliated with the University Museum at the University of Tokyo. Image adapted from research figure originally published in Systematic Biology, DOI: 10.1093/sysbio/syz024{module In-article}
North and south divide
This new analysis verified what earlier studies suggested: nonavian dinosaurs were divided into a group that lived in the Northern Hemisphere and another that lived in the Southern Hemisphere, and that those two groups could still move back and forth between Europe and Africa during the Early Cretaceous period (145 to 100 million years ago), but became isolated in the Late Cretaceous period (100 to 66 million years ago).

During the Early Cretaceous period, there were three major supercontinents: North America-Europe-Asia, South America-Africa, and Antarctica-India-Australia.

By the Late Cretaceous period, only the North America-Europe-Asia supercontinent remained. The other supercontinents had separated into the continents we know today, although they had not yet drifted to their current locations.

“During the Late Cretaceous period, high sea levels meant that Europe was a series of isolated islands. It makes sense that nonavian dinosaur species differentiated between Africa and Europe during that time,” said Kubo.

Kubo plans to complete additional biogeographical analyses for different time periods to continue tracking extinct species around the world and through time.

Turbulence responsible for black holes' balancing act

Tyler O'Neal, Staff Editor ACADEMIA
New simulations reveal that turbulence created by jets of material ejected from the disks of the Universe’s largest black holes is responsible for halting star formation. Evan Scannapieco, an assistant professor in the School of Earth and Space Exploration in the College of Liberal Arts and Sciences at Arizona State University (ASU) and Professor Marcus Brueggen of Jacobs University in Bremen, Germany, present the new model in a paper in the journal Monthly Notices of the Royal Astronomical Society.
 
We live in a hierarchical Universe where small structures join into larger ones. Earth is a planet in our Solar System, the Solar System resides in the Milky Way Galaxy, and galaxies combine into groups and clusters. Clusters are the largest structures in the Universe, but sadly our knowledge of them is not proportional to their size. Researchers have long known that the gas in the centres of some galaxy clusters is rapidly cooling and condensing, but were puzzled why this condensed gas did not form into stars. Until recently, no model existed that successfully explained how this was possible.
 
Professor Scannapieco has spent much of his career studying the evolution of galaxies and clusters. “There are two types of clusters: cool-core clusters and non-cool core clusters,” he explains. “Non-cool core clusters haven’t been around long enough to cool, whereas cool-core clusters are rapidly cooling, although by our standards they are still very hot.”
 
X-ray telescopes have revolutionized our understanding of the activity occurring within cool-core clusters. Although these clusters can contain hundreds or even thousands of galaxies, they are mostly made up of a diffuse, but very hot gas known as the intracluster medium. This intergalactic gas is only visible to X-ray telescopes, which are able to map out its temperature and structure. These observations show that the diffuse gas is rapidly cooling into the centres of cool-core clusters.
 
At the core of each of these clusters is a black hole, billions of times more massive than the Sun. Some of the cooling medium makes its way down to a dense disk surrounding this black hole, some of it goes into the black hole itself, and some of it is shot outward. X-ray images clearly show jet-like bursts of ejected material, which occur in regular cycles.
 
But why were these outbursts so regular, and why did the cooling gas never drop to colder temperatures that lead to the formation of stars? Some unknown mechanism was creating an impressive balancing act.
 
“It looked like the jets coming from black holes were somehow responsible for stopping the cooling,” says Scannapieco, “but until now no one was able to determine how exactly.”
 
Scannapieco and Brueggen used the enormous supercomputers at ASU to develop their own three-dimensional simulation of the galaxy cluster surrounding one of the Universe’s biggest black holes. By adapting an approach developed by Guy Dimonte at Los Alamos National Laboratory and Robert Tipton at Lawrence Livermore National Laboratory, Scannapieco and Brueggen added the component of turbulence to the simulations, which was never accounted for in the past.
 
And that was the key ingredient.
 
Turbulence works in partnership with the black hole to maintain the balance. Without the turbulence, the jets coming from around the black hole would grow stronger and stronger, and the gas would cool catastrophically into a swarm of new stars. When turbulence is accounted for, the black hole not only balances the cooling, but goes through regular cycles of activity.
 
“When you have turbulent flow, you have random motions on all scales,” explains Scannapieco. “Each jet of material ejected from the disk creates turbulence that mixes everything together.”
 
Scannapieco and Brueggen’s results reveal that turbulence acts to effectively mix the heated region with its surroundings so that the cool gas can’t make it down to the black hole, thus preventing star formation.
 
Every time some cool gas reaches the black hole, it is shot out in a jet. This generates turbulence that mixes the hot gas with the cold gas. This mixture becomes so hot that it doesn’t accrete onto the black hole. The jet stops and there is nothing to drive the turbulence so it fades away. At that point, the hot gas no longer mixes with the cold gas, so the centre of the cluster cools, and more gas makes its way down to the black hole.
 
Before long, another jet forms and the gas is once again mixed together.
 
“We improved our simulations so that they could capture those tiny turbulent motions,” explains Scannapieco. “Even though we can’t see them, we can estimate what they would do. The time it takes for the turbulence to decay away is exactly the same amount of time observed between the outbursts.”