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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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When it comes to biomolecules, RNA doesn’t get a lot of love.
Maybe you haven’t even heard of the silent workhorse. RNA is the cell’s de facto translator: like a game of telephone, RNA takes DNA’s genetic code to a cellular factory called ribosomes. There, the cell makes proteins based on RNA’s message.
But RNA isn’t just a middleman. It controls what proteins are formed. Because proteins wiz around the cell completing all sorts of important processes, you can say that RNA is the gatekeeper: no RNA message, no proteins, no life.
In a new study published in Nature, RNA finally took center stage. By adding bits of genetic material to the E. Coli bacteria, a team of biohackers at the Wyss Institute hijacked the organism’s RNA messengers so that they only spring into action following certain inputs.
The result? A bacterial biocomputer capable of performing 12-input logic operations—AND, OR, and NOT—following specific inputs. Rather than outputting 0s and 1s, these biocircuits produce results based on the presence or absence of proteins and other molecules.
“It’s the greatest number of inputs in a circuit that a cell has been able to process,” says study author Dr. Alexander Green at Arizona State University. “To be able to analyze those signals and make a decision is the big advance here.”
When given a specific set of inputs, the bacteria spit out a protein that made them glow neon green under fluorescent light.
But synthetic biology promises far more than just a party trick—by tinkering with a cell’s RNA repertoire, scientists may one day coax them to photosynthesize, produce expensive drugs on the fly, or diagnose and hunt down rogue tumor cells.
Illustration of an RNA-based ‘ribocomputing’ device that makes logic-based decisions in living cells. The long gate RNA (blue) detects the binding of an input RNA (red). The ribosome (purple/mauve) reads the gate RNA to produce an output protein. Image Credit: Alexander Green / Arizona State University
The software of life
This isn’t the first time that scientists hijacked life’s algorithms to reprogram cells into nanocomputing systems. Previous work has already introduced to the world yeast cells that can make anti-malaria drugs from sugar or mammalian cells that can perform Boolean logic.
Yet circuits with multiple inputs and outputs remain hard to program. The reason is this: synthetic biologists have traditionally focused on snipping, fusing, or otherwise arranging a cell’s DNA to produce the outcomes they want.
But DNA is two steps removed from proteins, and tinkering with life’s code often leads to unexpected consequences. For one, the cell may not even accept and produce the extra bits of DNA code. For another, the added code, when transformed into proteins, may not act accordingly in the crowded and ever-changing environment of the cell.
What’s more, tinkering with one gene is often not enough to program an entirely new circuit. Scientists often need to amp up or shut down the activity of multiple genes, or multiple biological “modules” each made up of tens or hundreds of genes.
It’s like trying to fit new Lego pieces in a specific order into a room full of Lego constructions. Each new piece has the potential to wander off track and click onto something it’s not supposed to touch.
Getting every moving component to work in sync—as you might have guessed—is a giant headache.
The RNA way
With “ribocomputing,” Green and colleagues set off to tackle a main problem in synthetic biology: predictability.
Named after the “R (ribo)” in “RNA,” the method grew out of an idea that first struck Green back in 2012.
“The synthetic biological circuits to date have relied heavily on protein-based regulators that are difficult to scale up,” Green wrote at the time. We only have a limited handful of “designable parts” that work well, and these circuits require significant resources to encode and operate, he explains.
RNA, in comparison, is a lot more predictable. Like its more famous sibling DNA, RNA is composed of units that come in four different flavors: A, G, C, and U. Although RNA is only single-stranded, rather than the double helix for which DNA is known for, it can bind short DNA-like sequences in a very predictable manner: Gs always match up with Cs and As always with Us.
Because of this predictability, it’s possible to design RNA components that bind together perfectly. In other words, it reduces the chance that added RNA bits might go rogue in an unsuspecting cell.
Normally, once RNA is produced it immediately rushes to the ribosome—the cell’s protein-building factory. Think of it as a constantly “on” system.
However, Green and his team found a clever mechanism to slow them down. Dubbed the “toehold switch,” it works like this: the artificial RNA component is first incorporated into a chain of A, G, C, and U folded into a paperclip-like structure.
This blocks the RNA from accessing the ribosome. Because one RNA strand generally maps to one protein, the switch prevents that protein from ever getting made.
In this way, the switch is set to “off” by default—a “NOT” gate, in Boolean logic.
To activate the switch, the cell needs another component: a “trigger RNA,” which binds to the RNA toehold switch. This flips it on: the RNA grabs onto the ribosome, and bam—proteins.
String a few RNA switches together, with the activity of each one relying on the one before, and it forms an “AND” gate. Alternatively, if the activity of each switch is independent, that’s an “OR” gate.
“Basically, the toehold switches performed so well that we wanted to find a way to best exploit them for cellular applications,” says Green. They’re “kind of the equivalent of your first transistors,” he adds.
Once the team optimized the designs for different logic gates, they carefully condensed the switches into “gate RNA” molecules. These gate RNAs contain both codes for proteins and the logic operations needed to kickstart the process—a molecular logic circuit, so to speak.
If you’ve ever played around with an Arduino-controlled electrical circuit, you probably know the easiest way to test its function is with a light bulb.
That’s what the team did here, though with a biological bulb: green fluorescent protein, a light-sensing protein not normally present in bacteria that—when turned on—makes the microbugs glow neon green.
In a series of experiments, Green and his team genetically inserted gate RNAs into bacteria. Then, depending on the type of logical function, they added different combinations of trigger RNAs—the inputs.
When the input RNA matched up with its corresponding gate RNA, it flipped on the switch, causing the cell to light up.
Their most complex circuit contained five AND gates, five OR gates, and two NOTs—a 12-input ribocomputer that functioned exactly as designed.
That’s quite the achievement. “Everything is interacting with everything else and there are a million ways those interactions could flip the switch on accident,” says RNA researcher Dr. Julies Lucks at Northwestern University.
The specificity is thanks to RNA, the authors explain. Because RNAs bind to others so predictably, we can now design massive libraries of gate and trigger units to mix-and-match into all types of nano-biocomputers.
Although the technology doesn’t have any immediate applications, the team has high hopes.
For the first time, it’s now possible to massively scale up the process of programming new circuits into living cells. We’ve expanded the library of available biocomponents that can be used to reprogram life’s basic code, the authors say.
What’s more, when freeze-dried onto a piece of tissue paper, RNA keeps very well. We could potentially print RNA toehold switches onto paper that respond to viruses or to tumor cells, the authors say, essentially transforming the technology into highly accurate diagnostic platforms.
But Green’s hopes are even wilder for his RNA-based circuits.
“Because we’re using RNA, a universal molecule of life, we know these interactions can also work in other cells, so our method provides a general strategy that could be ported to other organisms,” he says.
Ultimately, the hope is to program neural network-like capabilities into the body’s other cells.
Imagine cells endowed with circuits capable of performing the kinds of computation the brain does, the authors say.
Perhaps one day, synthetic biology will transform our own cells into fully programmable entities, turning us all into biological cyborgs from the inside. How wild would that be?
Image Credit: Wyss Institute at Harvard University Continue reading