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 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.
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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: http://bit.ly/1KUOwbF Journal of Molecular Biology, online
February 16, 2016.
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