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#437171 Scientists Tap the World’s Most ...
In The Hitchhiker’s Guide to the Galaxy by Douglas Adams, the haughty supercomputer Deep Thought is asked whether it can find the answer to the ultimate question concerning life, the universe, and everything. It replies that, yes, it can do it, but it’s tricky and it’ll have to think about it. When asked how long it will take it replies, “Seven-and-a-half million years. I told you I’d have to think about it.”
Real-life supercomputers are being asked somewhat less expansive questions but tricky ones nonetheless: how to tackle the Covid-19 pandemic. They’re being used in many facets of responding to the disease, including to predict the spread of the virus, to optimize contact tracing, to allocate resources and provide decisions for physicians, to design vaccines and rapid testing tools, and to understand sneezes. And the answers are needed in a rather shorter time frame than Deep Thought was proposing.
The largest number of Covid-19 supercomputing projects involves designing drugs. It’s likely to take several effective drugs to treat the disease. Supercomputers allow researchers to take a rational approach and aim to selectively muzzle proteins that SARS-CoV-2, the virus that causes Covid-19, needs for its life cycle.
The viral genome encodes proteins needed by the virus to infect humans and to replicate. Among these are the infamous spike protein that sniffs out and penetrates its human cellular target, but there are also enzymes and molecular machines that the virus forces its human subjects to produce for it. Finding drugs that can bind to these proteins and stop them from working is a logical way to go.
The Summit supercomputer at Oak Ridge National Laboratory has a peak performance of 200,000 trillion calculations per second—equivalent to about a million laptops. Image credit: Oak Ridge National Laboratory, U.S. Dept. of Energy, CC BY
I am a molecular biophysicist. My lab, at the Center for Molecular Biophysics at the University of Tennessee and Oak Ridge National Laboratory, uses a supercomputer to discover drugs. We build three-dimensional virtual models of biological molecules like the proteins used by cells and viruses, and simulate how various chemical compounds interact with those proteins. We test thousands of compounds to find the ones that “dock” with a target protein. Those compounds that fit, lock-and-key style, with the protein are potential therapies.
The top-ranked candidates are then tested experimentally to see if they indeed do bind to their targets and, in the case of Covid-19, stop the virus from infecting human cells. The compounds are first tested in cells, then animals, and finally humans. Computational drug discovery with high-performance computing has been important in finding antiviral drugs in the past, such as the anti-HIV drugs that revolutionized AIDS treatment in the 1990s.
World’s Most Powerful Computer
Since the 1990s the power of supercomputers has increased by a factor of a million or so. Summit at Oak Ridge National Laboratory is presently the world’s most powerful supercomputer, and has the combined power of roughly a million laptops. A laptop today has roughly the same power as a supercomputer had 20-30 years ago.
However, in order to gin up speed, supercomputer architectures have become more complicated. They used to consist of single, very powerful chips on which programs would simply run faster. Now they consist of thousands of processors performing massively parallel processing in which many calculations, such as testing the potential of drugs to dock with a pathogen or cell’s proteins, are performed at the same time. Persuading those processors to work together harmoniously is a pain in the neck but means we can quickly try out a lot of chemicals virtually.
Further, researchers use supercomputers to figure out by simulation the different shapes formed by the target binding sites and then virtually dock compounds to each shape. In my lab, that procedure has produced experimentally validated hits—chemicals that work—for each of 16 protein targets that physician-scientists and biochemists have discovered over the past few years. These targets were selected because finding compounds that dock with them could result in drugs for treating different diseases, including chronic kidney disease, prostate cancer, osteoporosis, diabetes, thrombosis and bacterial infections.
Scientists are using supercomputers to find ways to disable the various proteins—including the infamous spike protein (green protrusions)—produced by SARS-CoV-2, the virus responsible for Covid-19. Image credit: Thomas Splettstoesser scistyle.com, CC BY-ND
Billions of Possibilities
So which chemicals are being tested for Covid-19? A first approach is trying out drugs that already exist for other indications and that we have a pretty good idea are reasonably safe. That’s called “repurposing,” and if it works, regulatory approval will be quick.
But repurposing isn’t necessarily being done in the most rational way. One idea researchers are considering is that drugs that work against protein targets of some other virus, such as the flu, hepatitis or Ebola, will automatically work against Covid-19, even when the SARS-CoV-2 protein targets don’t have the same shape.
Our own work has now expanded to about 10 targets on SARS-CoV-2, and we’re also looking at human protein targets for disrupting the virus’s attack on human cells. Top-ranked compounds from our calculations are being tested experimentally for activity against the live virus. Several of these have already been found to be active.The best approach is to check if repurposed compounds will actually bind to their intended target. To that end, my lab published a preliminary report of a supercomputer-driven docking study of a repurposing compound database in mid-February. The study ranked 8,000 compounds in order of how well they bind to the viral spike protein. This paper triggered the establishment of a high-performance computing consortium against our viral enemy, announced by President Trump in March. Several of our top-ranked compounds are now in clinical trials.
Also, we and others are venturing out into the wild world of new drug discovery for Covid-19—looking for compounds that have never been tried as drugs before. Databases of billions of these compounds exist, all of which could probably be synthesized in principle but most of which have never been made. Billion-compound docking is a tailor-made task for massively parallel supercomputing.
Dawn of the Exascale Era
Work will be helped by the arrival of the next big machine at Oak Ridge, called Frontier, planned for next year. Frontier should be about 10 times more powerful than Summit. Frontier will herald the “exascale” supercomputing era, meaning machines capable of 1,000,000,000,000,000,000 calculations per second.
Although some fear supercomputers will take over the world, for the time being, at least, they are humanity’s servants, which means that they do what we tell them to. Different scientists have different ideas about how to calculate which drugs work best—some prefer artificial intelligence, for example—so there’s quite a lot of arguing going on.
Hopefully, scientists armed with the most powerful computers in the world will, sooner rather than later, find the drugs needed to tackle Covid-19. If they do, then their answers will be of more immediate benefit, if less philosophically tantalizing, than the answer to the ultimate question provided by Deep Thought, which was, maddeningly, simply 42.
This article is republished from The Conversation under a Creative Commons license. Read the original article.
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#432190 In the Future, There Will Be No Limit to ...
New planets found in distant corners of the galaxy. Climate models that may improve our understanding of sea level rise. The emergence of new antimalarial drugs. These scientific advances and discoveries have been in the news in recent months.
While representing wildly divergent disciplines, from astronomy to biotechnology, they all have one thing in common: Artificial intelligence played a key role in their scientific discovery.
One of the more recent and famous examples came out of NASA at the end of 2017. The US space agency had announced an eighth planet discovered in the Kepler-90 system. Scientists had trained a neural network—a computer with a “brain” modeled on the human mind—to re-examine data from Kepler, a space-borne telescope with a four-year mission to seek out new life and new civilizations. Or, more precisely, to find habitable planets where life might just exist.
The researchers trained the artificial neural network on a set of 15,000 previously vetted signals until it could identify true planets and false positives 96 percent of the time. It then went to work on weaker signals from nearly 700 star systems with known planets.
The machine detected Kepler 90i—a hot, rocky planet that orbits its sun about every two Earth weeks—through a nearly imperceptible change in brightness captured when a planet passes a star. It also found a sixth Earth-sized planet in the Kepler-80 system.
AI Handles Big Data
The application of AI to science is being driven by three great advances in technology, according to Ross King from the Manchester Institute of Biotechnology at the University of Manchester, leader of a team that developed an artificially intelligent “scientist” called Eve.
Those three advances include much faster computers, big datasets, and improved AI methods, King said. “These advances increasingly give AI superhuman reasoning abilities,” he told Singularity Hub by email.
AI systems can flawlessly remember vast numbers of facts and extract information effortlessly from millions of scientific papers, not to mention exhibit flawless logical reasoning and near-optimal probabilistic reasoning, King says.
AI systems also beat humans when it comes to dealing with huge, diverse amounts of data.
That’s partly what attracted a team of glaciologists to turn to machine learning to untangle the factors involved in how heat from Earth’s interior might influence the ice sheet that blankets Greenland.
Algorithms juggled 22 geologic variables—such as bedrock topography, crustal thickness, magnetic anomalies, rock types, and proximity to features like trenches, ridges, young rifts, and volcanoes—to predict geothermal heat flux under the ice sheet throughout Greenland.
The machine learning model, for example, predicts elevated heat flux upstream of Jakobshavn Glacier, the fastest-moving glacier in the world.
“The major advantage is that we can incorporate so many different types of data,” explains Leigh Stearns, associate professor of geology at Kansas University, whose research takes her to the polar regions to understand how and why Earth’s great ice sheets are changing, questions directly related to future sea level rise.
“All of the other models just rely on one parameter to determine heat flux, but the [machine learning] approach incorporates all of them,” Stearns told Singularity Hub in an email. “Interestingly, we found that there is not just one parameter…that determines the heat flux, but a combination of many factors.”
The research was published last month in Geophysical Research Letters.
Stearns says her team hopes to apply high-powered machine learning to characterize glacier behavior over both short and long-term timescales, thanks to the large amounts of data that she and others have collected over the last 20 years.
Emergence of Robot Scientists
While Stearns sees machine learning as another tool to augment her research, King believes artificial intelligence can play a much bigger role in scientific discoveries in the future.
“I am interested in developing AI systems that autonomously do science—robot scientists,” he said. Such systems, King explained, would automatically originate hypotheses to explain observations, devise experiments to test those hypotheses, physically run the experiments using laboratory robotics, and even interpret the results. The conclusions would then influence the next cycle of hypotheses and experiments.
His AI scientist Eve recently helped researchers discover that triclosan, an ingredient commonly found in toothpaste, could be used as an antimalarial drug against certain strains that have developed a resistance to other common drug therapies. The research was published in the journal Scientific Reports.
Automation using artificial intelligence for drug discovery has become a growing area of research, as the machines can work orders of magnitude faster than any human. AI is also being applied in related areas, such as synthetic biology for the rapid design and manufacture of microorganisms for industrial uses.
King argues that machines are better suited to unravel the complexities of biological systems, with even the most “simple” organisms are host to thousands of genes, proteins, and small molecules that interact in complicated ways.
“Robot scientists and semi-automated AI tools are essential for the future of biology, as there are simply not enough human biologists to do the necessary work,” he said.
Creating Shockwaves in Science
The use of machine learning, neural networks, and other AI methods can often get better results in a fraction of the time it would normally take to crunch data.
For instance, scientists at the National Center for Supercomputing Applications, located at the University of Illinois at Urbana-Champaign, have a deep learning system for the rapid detection and characterization of gravitational waves. Gravitational waves are disturbances in spacetime, emanating from big, high-energy cosmic events, such as the massive explosion of a star known as a supernova. The “Holy Grail” of this type of research is to detect gravitational waves from the Big Bang.
Dubbed Deep Filtering, the method allows real-time processing of data from LIGO, a gravitational wave observatory comprised of two enormous laser interferometers located thousands of miles apart in California and Louisiana. The research was published in Physics Letters B. You can watch a trippy visualization of the results below.
In a more down-to-earth example, scientists published a paper last month in Science Advances on the development of a neural network called ConvNetQuake to detect and locate minor earthquakes from ground motion measurements called seismograms.
ConvNetQuake uncovered 17 times more earthquakes than traditional methods. Scientists say the new method is particularly useful in monitoring small-scale seismic activity, which has become more frequent, possibly due to fracking activities that involve injecting wastewater deep underground. You can learn more about ConvNetQuake in this video:
King says he believes that in the long term there will be no limit to what AI can accomplish in science. He and his team, including Eve, are currently working on developing cancer therapies under a grant from DARPA.
“Robot scientists are getting smarter and smarter; human scientists are not,” he says. “Indeed, there is arguably a case that human scientists are less good. I don’t see any scientist alive today of the stature of a Newton or Einstein—despite the vast number of living scientists. The Physics Nobel [laureate] Frank Wilczek is on record as saying (10 years ago) that in 100 years’ time the best physicist will be a machine. I agree.”
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