Online gamers beat supercomputers at RNA modeling

(Reuters Health) - Online gamers have uncovered better models for folding RNA molecules than supercomputers housed in some of the world’s most prestigious research labs, according to a new report.

The interactive game, Eterna, challenges players to design chemical sequences of RNA that fold stably into desired shapes.

An online community of more than 100,000 registered Eterna players discovered features of RNA molecules that make folding them simple or difficult.

This matters, researchers say, because understanding the secrets to RNA design may speed development of new antibiotics, vaccines and treatments for disease.

“RNA molecules provide a kind of `operating system’ for cells and viruses, and so their behaviors have to be understood if we want to control cancer, viral infection and other diseases with molecular precision,” said senior study author Rhiju Das, a biochemist at Stanford University in California.

“Designed RNA molecules suggest a new route to therapies customized to particular patients, infections or cancers – but there’s still a lot of research to do before we get there,” Das added by email.

Das and Adrien Treuille, a computer scientist at Carnegie Mellon University in Pittsburgh, launched Eterna in 2011. From the start, they allowed any gamer age 13 or older to play – no special skills or biochemistry training required.

To understand what factors may influence the shape of RNA, players solved folding puzzles in the game.

Experienced gamers rated the difficulty of creating different shapes to guide new players from easier to harder puzzles.

Then - highlighting the potential for crowdsourcing to transform scientific discovery - the gamers compiled a list of features that made RNA shapes the most challenging to create and asked scientists in Das’ lab to test the reliability of their system ranking designs from simple to nearly impossible.

Stanford scientists used supercomputers to test the players’ predictions against a half-dozen algorithms developed to supply RNA sequences that fold into specific shapes.

The Eterna players solved most puzzles and rated the difficulty of different designs as well as the computers did, Das and colleagues report in the Journal of Molecular Biology.

But for the most vexing puzzles the gamers solved, the machines remained stumped even after devoting several days of computing time to the search for a solution.

While the players who helped author the paper on RNA folding are largely self-taught, and come from a variety of educational backgrounds, Das described them as “citizen scientists.”

“This work indicates that online gamers can actually take the lead on defining research questions and write up their own results,” Das said. “Those have traditionally been the role of academically trained scientists.”

Previous game-based research has helped scientists learn something about the players, but the Eterna project takes a different approach in crowd-sourcing data analysis to answer questions unrelated to the people playing the game, said Dr. Adam Gazzaley, a neurology researcher at the University of California, San Francisco, who wasn’t involved in the study.

“Although most players may not have scientific training, they may indeed have skills (e.g. logic, spatial manipulation) that make them valuable,” Gazzaley said by email. “There is great potential for widely distributed games played by large numbers of individuals around the world to aid the scientific discovery process.”

Even without a science background, experienced gamers may have the insight and problem-solving skills needed to navigate this type of RNA design puzzle, said Craig Stark, a neurobiologist at the University of California, Irvine, who wasn’t involved in the study.

“People are smart and creative and if we can harness this power, we have a tremendous tool at our disposal,” Stark said by email.

SOURCE: Journal of Molecular Biology, online February 16, 2016.