Machine learning used to understand and predict dynamics of worm behavior

The roundworm C. elegans is a well-established laboratory model system. While the worm is a fairly simple living system, it is complicated enough to serve as "a kind of sandbox" for testing out methods of automated inference, says Emory biophysicist Ilya Nemenman. (Getty Images)

By Carol Clark

Biophysicists have used an automated method to model a living system — the dynamics of a worm perceiving and escaping pain. The Proceedings of the National Academy of Sciences (PNAS) published the results, which worked with data from experiments on the C. elegans roundworm.

“Our method is one of the first to use machine-learning tools on experimental data to derive simple, interpretable equations of motion for a living system,” says Ilya Nemenman, senior author of the paper and a professor of physics and biology at Emory University. “We now have proof of principle that it can be done. The next step is to see if we can apply our method to a more complicated system.”

The model makes accurate predictions about the dynamics of the worm behavior, and these predictions are biologically interpretable and have been experimentally verified.

Collaborators on the paper include first author Bryan Daniels, a theorist from Arizona State University, and co-author William Ryu, an experimentalist from the University of Toronto.

The researchers used an algorithm, developed in 2015 by Daniels and Nemenman, that teaches a computer how to efficiently search for the laws that underlie natural dynamical systems, including complex biological ones. They dubbed the algorithm “Sir Isaac,” after one of the most famous scientists of all time — Sir Isaac Newton. Their long-term goal is to develop the algorithm into a “robot scientist,” to automate and speed up the scientific method of forming quantitative hypotheses, then testing them by looking at data and experiments.

While Newton’s Three Laws of Motion can be used to predict dynamics for mechanical systems, the biophysicists want to develop similar predictive dynamical approaches that can be applied to living systems.

For the PNAS paper, they focused on the decision-making involved when C. elegans responds to a sensory stimulus. The data on C. elegans had been previously gathered by the Ryu lab, which develops methods to measure and analyze behavioral responses of the roundworm at the holistic level, from basic motor gestures to long-term behavioral programs.

C. elegans is a well-established laboratory animal model system. Most C. elegans have only 302 neurons, few muscles and a limited repertoire of motion. A sequence of experiments involved interrupting the forward movement of individual C. elegans with a laser strike to the head. When the laser strikes a worm, it withdraws, briefly accelerating backwards and eventually returning to forward motion, usually in a different direction. Individual worms respond differently. Some, for instance, immediately reverse direction upon laser stimulus, while others pause briefly before responding. Another variable in the experiments is the intensity of the laser: Worms respond faster to hotter and more rapidly rising temperatures.

For the PNAS paper, the researchers fed the Sir Isaac platform the motion data from the first few seconds of the experiments — before and shortly after the laser strikes a worm and it initially reacts. From this limited data, the algorithm was able to capture the average responses that matched the experimental results and also to predict the motion of the worm well beyond these initial few seconds, generalizing from the limited knowledge. The prediction left only 10 percent of the variability in the worm motion that can be attributed to the laser stimulus unexplained. This was twice as good as the best prior models, which were not aided by automated inference.

“Predicting a worm’s decision about when and how to move in response to a stimulus is a lot more complicated than just calculating how a ball will move when you kick it,” Nemenman says. “Our algorithm had to account for the complexities of sensory processing in the worms, the neural activity in response to the stimuli, followed by the activation of muscles and the forces that the activated muscles generate. It summed all this up into a simple and elegant mathematical description.”

The model derived by Sir Isaac was well-matched to the biology of C. elegans, providing interpretable results for both the sensory processing and the motor response, hinting at the potential of artificial intelligence to aid in discovery of accurate and interpretable models of more complex systems.

“It’s a big step from making predictions about the behavior of a worm to that of a human,” Nemenman says, “but we hope that the worm can serve as a kind of sandbox for testing out methods of automated inference, such that Sir Isaac might one day directly benefit human health. Much of science is about guessing the laws that govern natural systems and then verifying those guesses through experiments. If we can figure out how to use modern machine learning tools to help with the guessing, that could greatly speed up research breakthroughs.”

Related:
Biophysicists take small step in quest for 'robot scientist'
Physicists eye neural fly data, find formula for Zipf's law
Biology may not be so complex after all

A nod to World Sleep Day

World Sleep Day is March 15 this year. The annual event is a celebration of sleep and a call to action on issues related to sleep, including medicine, education and social aspects.

In Emory anthropologist Carol Worthman's research around the world, "sleep has emerged as both more flexible and more social than one would think from the perspective of the West," writes Todd Pitock in Aeon Magazine.

"When Worthman started exploring the anthropology of sleep more than a decade ago," the article continues, "the topic was way below the radar of colleagues who believed that culture was something you did while awake. But she found otherwise."

Read the whole article here.

Related:
Some eye-opening thoughts on sleep
What literature can teach us about sleep

The importance of puberty: A call for better research models

“Due to the global slowdown in fertility, this is probably the biggest cohort of young people we will ever see,” says anthropologist Carol Worthman. “If we are ever going to get serious about helping adolescents reach their full potential, now is the time.”

By Carol Clark

Puberty is much more than just a time of biological overdrive, propelled by sexual maturation. Progress in developmental science has greatly broadened the perspective of this critical maturational milestone.

“We’ve moved beyond thinking of puberty as simply raging hormones,” says Carol Worthman, professor of anthropology at Emory University. “Major advances in understanding of brain development clearly show that the sociological and psychological impacts during puberty are just as important as the hormones.”

What’s needed now, Worthman argues as lead author on a new paper, is to integrate this understanding into more comprehensive research models. The Journal of Research on Adolescence published the paper, which reviews key theories and methods that are relevant to studies of puberty.

“Puberty was once thought of as the biological process of teen development and adolescence was considered the cultural process,” Worthman says. “We want to raise awareness that bracketing research in this way is no longer a useful approach.”

For decades, researchers have focused on improving the health of infants and children, resulting in substantial declines in child mortality worldwide.

While babies and children are labeled as cute and positive, full of possibility, adolescents are more often seen as problems. They have generally been less studied, Worthman says, even though the second decade of life is a critical time when risks spike for the development of mental illness, substance abuse and the escalation of injuries. And what happens in puberty, she adds, impacts health and well-being across the lifespan.

The global population is now bulging with young people aged 10 to 19, who today number more than 1.2 billion, or 17 percent of humanity. These young people must deal with finding their way into adulthood amid massive, rapid social transformations.

“Due to the global slowdown in fertility, this is probably the biggest cohort of young people we will ever see,” Worthman says. “If we are ever going to get serious about helping adolescents reach their full potential, now is the time.”

In her own research, Worthman uses a biocultural approach to conduct comparative interdisciplinary studies of human development. Samatha Dockray, a co-author of the paper from University College Cork, studies psychobiological mechanisms to understand their effects on adolescent health and behavior. The third co-author, Kristine Marceau from Purdue University, integrates genetics, prenatal risk, neuroendocrine development and the family environment into her developmental research.

The paper outlines minimally invasive methods to study different aspects of puberty. For instance, hair and fingernail clippings can be used to track stress levels and hormones over time. Changes in the microbiome, immune function and brain are other critical aspects of puberty that can be measured, along with cognition, behavior and ecological contexts.

“By taking advantage of new methods, and working in interdisciplinary teams, developmental scientists can explore more questions about adolescent development and welfare in more integrated ways,” Worthman says.

The review paper is part of a special section on puberty published by the Journal of Research on Adolescence. Topics covered include emerging genetic-environmental complexities of puberty, the role of puberty in the developing brain, how puberty impacts health and well-being across the lifespan and the need to explore puberty in understudied populations.

Related:
Scientists zeroing in on psychosis risk factors

Changes in rat size reveal habitat of 'Hobbit' hominin

At the Liang Bua cave site, paleoanthropologist Matthew Tocheri, left, measures a modern giant rat with the assistance of Bonefasius Sagut. At right is a reconstruction of Homo floresiensis carrying a giant rat, by paleo artist Peter Schouten.

By Carol Clark

A study of rat body sizes shifting over time gives a glimpse into the habitat of the mysterious hominin Homo floresiensis — nicknamed the “Hobbit” due to its diminutive stature.

The Journal of Human Evolution is publishing the study, based on an analysis of thousands of rodent bones, mainly fore- and hind-limbs, from an Indonesian cave where H. floresiensis was discovered in 2003. The results indicate that the local habitat was mostly open grasslands more than 100,000 years ago, but began shifting rapidly to a more closed environment 60,000 years ago.

“Our paper is the first that we know of to use the leg bones of rats in this way to interpret ecological change through time, and it provides new evidence for the local environment during the time of Homo Floresiensis,” says Elizabeth Grace Veatch, a PhD candidate at Emory University and a first author of the study.

Veatch with an H. floresiensis skull.

H. floresiensis stood only about 3 feet 6 inches tall and was known to have lived about 190,000 to 50,000 years ago on the oceanic island of Flores in eastern Indonesia. The tiny hominin shared the island with animals that could have come from the pages of a Tolkien novel, including giant Komodo dragons, six-foot-tall storks, vultures with a six-foot wingspan, and pygmy Stegodons — herbivores that looked like small elephants with swooping, oversized tusks.

It was the rats, however, that most interested Veatch.

Murids, as the rat family is known, are more taxonomically diverse than any other mammal group and are found in nearly every part of the world. “They exhibit an incredible range of behaviors occupying many different ecological niches,” Veatch says. “And because small mammals are typically sensitive to ecological shifts, they can tell you a lot about what’s going on in an environment.”

The study was based on remains recovered from the limestone cave known as Liang Bua, where partial skeletons of H. floresiensis have been found, along with stone tools and the remains of animals — most of them rats. In fact, out of the 275,000 animal bones identified in the cave so far, 80 percent of them are from rodents.

Veatch came to Emory to work with paleoanthropologist Jessica Thompson, a leading expert in using taphonomy — the study of what happens to bones after an organism dies — to learn more about the evolution of the human diet. Although Thompson has now moved to Yale University, she continues to mentor Veatch in her graduate studies at Emory.

Veatch became part of the Liang Bua project while doing an internship with the Human Origins Program of the Smithsonian Institution’s National Museum of Natural History. Her mentor there was paleoanthropologist Matthew Tocheri (now with Lakehead University in Ontario) who shares first-authorship of the current paper with Veatch.

“Matthew asked me if I wanted to analyze some rat bones and I said, ‘Sure,’” Veatch recalls. “I had no idea what I was getting into.”

A graphic of the rat species included in the study.

The study encompassed about 10,000 of the Liang Bua rat bones. The remains spanned five species with distinct sizes, from the mouse-sized Rattus hainaldi up to the housecat-sized Papagomys armandvillei — commonly known as the Flores giant rat. After categorizing the bones, the researchers could then directly link them to both species and environmental types.

While rats can adjust to new environments, the morphologies of different species tend to be adaptive to their preferred environment. For example, the habitat of the medium-sized Komodomys rintjanus, included in the study, is primarily open grasslands intermittent with patches of forest. In contrast, the tiny R. hainaldi and the giant P. armandvillei both prefer more closed or semi-closed forested habitats.

Tracking the relative abundances of the different rat species over time indicated that the local ecology was mostly open grassland 100,000 years ago, transitioning to a more-closed, forested habitat around 60,000 years ago. That is around the same time that skeletal elements belonging to Homo floresiensis, the pygmy Stegodon, giant storks, vulture and Komodo dragons disappear from Liang Bua.

“The evidence suggests that Homo floresiensis may have preferred more open habitats where they may have been a part of this scavenging guild of Stegodons, storks and vultures,” Veatch says. “We think that when the habitat changed, becoming more forested, Homo floresiensis probably left the Liang Bua area, tracking these animals to more open habitats elsewhere on the island.”

Veatch looks at piles of sediment excavated from Luang Bua as it is being wet sieved using the irrigation system of a rice paddy near the cave site.

Many more mysteries remain regarding H. floresiensis, Veatch says, and the Liang Bua rat bones may help solve some of them. One key question is whether H. floresiensis hunted small game.

“Our early ancestors adapted to consuming large amounts of big game through hunting or scavenging — or both,” Veatch says. “Big game undoubtedly became a critical food source, resulting in numerous social and physiological adaptations, including social cooperation and brain expansion. It’s much less known, however, what role small-game hunting may have played in our early evolution — if any at all.”

Liang Bua, she says, offers an ideal opportunity to study what a small-brained hominin, like H. floresiensis, might hunt if it had both sources of big game, like the Stegodon, and small game, like the giant Flores rat and other rat species.

Veatch is conducting field studies at the Liang Bua site, including running experiments to determine how difficult it would be to capture wild Flores rats. She is also doing research at the Pusat Penelitian Arkeologi Nasional (ARKENAS) Museum in the Indonesian capital of Jakarta where many of the bones from the cave site are now stored. She is analyzing a large sample of the bones to determine if any have cut marks — indicating butchering with tools — or pitted marks that would indicate they were digested by owls or other raptors that may have deposited them in the cave.

“In Indonesia, my nickname is Miss Tikus, which means ‘Miss Rat,’” Veatch says. “I’m perfectly fine with that because rats are really intelligent and extraordinary animals. We see them through the entire sequence in the archeology of Liang Bua and we will continue to use them in future studies to learn more about what went on in the cave.”

Co-authors of the current paper include Thomas Sutikna, E. Wahyu Saptomo and Jamiko, who are all from ARKENAS and the University of Wollongong in Australia; Kate McGrath from the University of Bordeaux, France; and Kristofer Helgen from the University of Adelaide in Australia.

Photo credits: All images courtesy of the Liang Bua research team. Photo of Veatch with skull was taken by Kristofer Helgen. The photo of Veatch and sediment was taken by Hanneke Meijer.

Related:
Bonding over bones, stones and beads
Malawi yields oldest known DNA from Africa

From Stone Age chips to microchips: How tiny tools made us human

Tiny stone flakes such as the one above, from a site in South Africa called Boomplaas, may have helped some humans survive the last period of rapid climate change, 17,000 years ago, says Emory anthropologist Justin Pargeter.

Anthropologists have long made the case that tool-making is one of the key behaviors that separated our human ancestors from other primates. A new paper, however, argues that it was not tool-making that set hominins apart — it was the miniaturization of tools.

Just as tiny transistors transformed telecommunications a few decades ago, and scientists are now challenged to make them even smaller, our Stone Age ancestors felt the urge to make tiny tools. “It’s a need that we’ve been perennially faced with and driven by,” says Justin Pargeter, an anthropologist at Emory University and lead author of the paper. “Miniaturization is the thing that we do.”

The journal Evolutionary Anthropology is publishing the paper — the first comprehensive overview of prehistoric tool miniaturization. It proposes that miniaturization is a central tendency in hominin technologies going back at least 2.6 million years.

Learn more by clicking here.