By Deborah Borfitz

November 4, 2020 | Gaming and sciencetwo seemingly incompatible areas of activityhave come together nicely in the case of citizen science games such as Foldit, Phylo, and Borderlands Science, as reported by academics close to the action who presented at the recent Bio-IT World Conference & Expo Virtual. The games are all played online, involve analyzing large sets of data, and endeavoring to solve real scientific problems. And players get credit individually (when willing) or as a crowd when findings appear in scholarly, peer-reviewed publications.

Whats not to love about the concept? Its certainly a great way to redirect the attention of people already spending untold hours on video games, says Seth Cooper, assistant professor in the Khoury College of Computer Sciences at Northeastern University. A pioneer of the field of scientific discovery games, he has demonstrated that video game enthusiasts are able to outperform purely computational methods for certain types of structural biochemistry problems, effectively codify their strategies, and integrate with the lab to help design real synthetic proteins.

Cooper is co-creator of Foldit, where the competition is about protein folding and design. Its hard for a computer to search all the possibilities without the aid of human creativity and reason, he says. The game is built on chemistry software called Rosetta and has been out for over a decade with more than half a million players, Cooper continues. It has evolved into a multi-institutional collaboration.

The goal, as with most games, is to get a high score, Cooper says. Players compete, and often collaborate, to build the best protein structures.

The process begins with a biochemist identifying a problem that gets turned into a game or puzzle that gets posted online, he explains. Each puzzle is only available for about a week, and generally a couple are up for play at any one time. Data generated by the Foldit players continually improve the game for better scientific results, Cooper notes. The levels of play get progressively harder.

Anyone can participate and most have no formal background in biochemistry, yet theyre contributing to science, he says. Back in 2011, players famously came up with an elegant, low-energy model for a monkey-virus enzyme, solving a longstanding scientific problem potentially useful for the design of retroviral drugs for AIDSand accomplished the feat inside of three weeks.

Players have also successfully redesigned existing enzymes, Cooper adds, as well as designed several protein structures from scratch that have been confirmed by X-ray crystallography. Theyre now working on designing an enzyme that will bind to the spike protein of SARS-CoV-2.

Vanderbilt University is also using Foldit to design small molecules and the University of California, Davis is studying the impact of adding a narrative to the competition. In the future, Cooper says, Foldit users might start working in a virtual reality environment. An educational version of Foldit with more contextual science information is available for classroom use, says Cooper, as is a standalone version that is completely separate from the game.

Burning Task Use

At McGill University, associate professor and computational scientist Jerome Waldispuehl is championing the gamification of genomics research with citizen science video game Phylo and its newest iteration called Borderlands Science. His focus is on multiple sequence alignment, one of the most challenging problems in bioinformatics that involves discovering similarities between a set of protein or DNA sequences.

Phylo presents players with DNA puzzles where they manipulate patterns consisting of colored tiles so that they almost forget the scientific context, Waldispuehl says. The abstraction task is to minimize the mismatch of colors to avoid a penalty.

Every alignment submitted by players is eventually reinserted into an existing algorithm as an optimization, says Waldispuehl. Alignments up for play contain sections of human DNA thought to be linked to various genetic disorders. Since 2010, Phylo has had 350,000 participants and generated one million solutions by improving alignments by 40%-95% over a computer algorithm, he reports.

Borderlands Science, launched in April for purposes of education and science outreach, quickly hit the one million mark with players and has come up with 50 million solutions, he adds. Collaborators include video game science company Massively Multiplayer Online Science, Gearbox Software and The Microsetta Initiative of the University of California, San Diego.

The Borderlands version of the game is played vertically rather than horizontally and rewards success with in-game currency that is important to some players, Waldispuehl says. It is currently aimed at improving 16S ribosomal RNA gene sequences from human microbiome alignments.

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Real Progress In Crowdsourcing Scientific Tasks To Gamers - Bio-IT World