249:, an initiative to develop a new diagnostic device for tuberculosis. The project uses a gene expression "signature" discovered by Stanford researchers using public data, and aims to create an open source, paper-based diagnostic kit that can be easily deployed in clinics around the world. The development of the open source kit is a collaboration with MIT's
27:
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level, and used the results to design structured nanoluciferases that were tested for degradation in vitro and for protein expression in vivo. The OpenVaccine research resulted in novel methods and principles for designing stabilized mRNA therapeutics, including vaccines with potentially three times the current shelf life.
302:
designed by the players identified specific structural features that make inverse RNA folding difficult. The Eterna researchers hope that by integrating their strategies into algorithms, improvement in automated RNA secondary structure design can be achieved. The results of the challenges were published in the
232:
Eterna puzzles are roughly classified into three types: Challenges, Player
Puzzles, and Cloud Lab. Challenges are the puzzles prepared by the game-makers to introduce players to the workings of Eterna as well as to provide series of pre-set puzzles for players to attempt. Player puzzles are generated
264:
In response to the SARS-CoV-2 epidemic, Eterna joined the OpenVaccine collaboration to develop methods for stabilizing mRNA molecules that could be stored and shipped without the need for deep freezing. Players submitted 6000 designs for probing the stability of small RNA molecules at the nucleotide
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New players are guided through an initial puzzle progression which introduces the basic concepts of RNA structure and folding. As players proceed through puzzles of increasing complexity, the different game interface elements are described. After completing the 30 puzzles and earning all five Eterna
228:
with the RNA and has critical effects on the free energy of the system. In some more advanced puzzles, players may be presented with two or three different target shapes at the same time; the single sequence the player produces must fold in the respective shapes under different conditions (presence
273:
In 2019, Eterna launched the ribosome engineering project OpenRibosome in collaboration with the Jewett Lab at
Northwestern University to enhance the folding of modified Escherichia coli ribosomes on the iSAT cell-free ribosome construction platform. The protein production of twenty 16S and twenty
260:
in August 2017, which challenges players to design single guide RNAs (sgRNAs) used in CRISPR gene editing. The goal of the project is to create a new class of sgRNAs that can be modulated by another small molecule (such as theophylline), allowing gene editing in the body to be turned on or off as
301:
The Eterna gamers beat the supercomputer-powered algorithms in solving all the 100 RNA secondary structure design challenges, while the best score of the six algorithms used is 54. By manipulating the chemical sequences of RNA the gamers created stable forms of desired shapes. The strategies
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Ultimately, Eterna researchers hope to determine a "complete and repeatable set of rules" to allow the synthesis of RNAs that consistently fold in expected shapes. Eterna project leaders hope that determining these basic principles may facilitate the design of RNA-based
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Essentials badges, players gain access to the Cloud Lab where they can participate in laboratory research. Once players have completed a sufficient number of RNA puzzles, they unlock the chance to generate puzzles for other players.
174:. Eterna creators have been pleasantly surprised by the solutions of Eterna players, particularly those of non-researchers whose "creativity isn't constrained by what they think a correct answer should look like".
615:
Wayment-Steele, Hannah K; Kim, Do Soon; Choe, Christian A; Nicol, John J; Wellington-Oguri, Roger; Watkins, Andrew M; Parra
Sperberg, R Andres; Huang, Po-Ssu; Participants, Eterna; Das, Rhiju (2021-09-14).
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23S sequences designed by players are being evaluated in a series of four feedback-based iterations. The ribosomes are being reengineered as molecular machines capable of synthesizing unique polymers.
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in
February 2016. This was the first paper based on dominant writing contributions—and co-lead authorship—by non-expert citizen scientists recruited through a video game.
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Eterna citizen scientists discovered a discrepancy in SHAPE and DMS chemical probing when reading strings of 7+ adenosine, and subsequently published their findings in
253:. Players successfully designed RNAs to detect the gene signature by round 2 of the challenge, and as of February 2018 testing continues with real patient samples.
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in a
Stanford biochemistry lab to evaluate the folding patterns of the RNA molecules to compare directly with the computer predictions, ultimately improving the
951:
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needed. At the conclusion of round 1 in
November 2017, players had submitted over 90,000 RNA designs for synthesis, the largest set of submissions to date.
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of the system and dramatically affect the RNA strand's folding dynamics. In Eterna, different restrictions, such as those on the number of certain
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Players are presented with a given target shape into which an RNA strand must fold. The player can change the sequence by placing any of the four
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by players, and Cloud Lab is where the active, proposed and archived laboratory projects are presented for players to review, vote or attempt.
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capabilities to solve puzzles that are computationally laborious for current computer models. The researchers hope to capitalize on "
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By August 2011, approximately 26,000 players had contributed RNA sequence designs and over 306 designs have been synthesized for
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Wellington-Oguri, Roger; Fisker, Eli; Zada, Mathew; Wiley, Michelle; Townley, Jill; Players, Eterna (2020-06-09).
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Lee, Jeehyung; Kladwang, Wipapat; Lee, Minjae; Cantu, Daniel; Azizyan, Martin; Kim, Hanjoo; Limpaecher, Alex;
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315:. It is the first paper written exclusively by citizen scientists to be published in a peer-reviewed journal.
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of Eterna players to answer fundamental questions about RNA folding mechanics. The top voted designs are
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142:—created by some of the same researchers that developed Eterna—the puzzles take advantage of human
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841:"Evidence of an Unusual Poly(A) RNA Signature Detected by High-Throughput Chemical Mapping"
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618:"Theoretical basis for stabilizing messenger RNA through secondary structure design"
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481::Interview with Adrien Treuille, Byron Spice, Faculty & Staff News,
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687:"The Public, Playing a Molecule-Building Game, Outperforms Scientists"
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journal, with "Eterna participants" listed as co-authors in the paper.
792:"Principles for Predicting RNA Secondary Structure Design Difficulty"
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205:
171:
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731:; Treuille, Adrien; Das, Rhiju; Eterna participants (Jan 17, 2014).
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In
January 2014, the results from Eterna have been published in the
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494:
472:"Treuille On Eterna - A Game Played By Humans, Scored By Nature"
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In 2016, Eterna launched its first biomedical challenge called
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Anderson-Lee, J.; Fisker, E.; et al. (17 February 2016).
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540:"Gamers crush algorithms in RNA structure design challenge"
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types, as well as locked bases, are sometimes imposed. A
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As of 2016, Eterna has about 250,000 registered players.
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American
Society for Biochemistry and Molecular Biology
115:, that engages users to solve puzzles related to the
368:"RNA Game Lets Players Help Find a Biological Prize"
81:
65:
57:
49:
33:
733:"RNA design rules from a massive open laboratory"
256:Following the success of OpenTB, Eterna launched
506:"Will NIH Embrace Biomedical Research Prizes?"
590:"Online Gamers Could Help Vaccinate Billions"
8:
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208:) at various positions; this can alter the
123:molecules. The project is supported by the
962:Video games developed in the United States
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18:
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649:
533:
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436:"RNA research Eterna gets its game on"
408:
406:
689:, Rachel Wiseman, Wired Campus blog,
363:
361:
224:is occasionally also included, which
7:
952:Carnegie Mellon University software
454:"Play a game and engineer real RNA"
229:or absence of a binding molecule).
707:"Eterna results published in PNAS"
14:
692:The Chronicle of Higher Education
538:Taylor, Nick (18 February 2016).
125:Bill and Melinda Gates Foundation
127:, Stanford University, and the
341:List of crowdsourcing projects
1:
937:Human-based computation games
129:National Institutes of Health
107:, developed by scientists at
16:2010 browser-based video game
796:Journal of Molecular Biology
674:"OpenRibosome Lab Challenge"
413:"Rebooting science outreach"
305:Journal of Molecular Biology
216:and the number of the three
131:. Prior funders include the
857:10.1021/acs.biochem.0c00215
133:National Science Foundation
978:
576:"OpenCRISPR Lab Challenge"
483:Carnegie Mellon University
387:"Eterna - Invent Medicine"
109:Carnegie Mellon University
44:Carnegie Mellon University
808:10.1016/j.jmb.2015.11.013
24:
802:(5). Elsevier: 748–757.
758:10.1073/pnas.1313039111
441:San Francisco Chronicle
152:collective intelligence
622:Nucleic Acids Research
562:"OpenTB Lab Challenge"
542:. fiercebiotechit.com
241:Biomedical challenges
105:"game with a purpose"
957:Stanford University
749:2014PNAS..111.2122L
634:10.1093/nar/gkab764
628:(18): 10604–10617.
336:Game with a purpose
113:Stanford University
72:Game with a purpose
40:Stanford University
21:
942:Puzzle video games
511:2011-07-26 at the
485:, January 22, 2011
477:2012-10-04 at the
462:, January 11, 2011
444:, January 17, 2011
418:2018-07-18 at the
376:, January 10, 2011
373:The New York Times
251:Little Devices Lab
851:(22): 2041–2046.
695:, August 12, 2011
596:. 15 October 2020
515:, Michael Price,
269:Synthetic biology
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927:2010 video games
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900:Official website
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144:problem-solving
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50:Initial release
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391:eternagame.org
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544:. Retrieved
525:19 July 2011
521:
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501:
495:About Eterna
490:
467:
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394:. Retrieved
390:
381:
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346:Serious game
313:Biochemistry
312:
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168:nanomachines
164:
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58:Available in
35:Developer(s)
907:Eterna Wiki
600:13 November
546:23 February
426:, June 2011
210:free energy
190:nucleotides
156:synthesized
138:Similar to
916:Categories
396:2018-02-07
352:References
258:OpenCRISPR
150:" and the
87:eternagame
881:218649394
865:0006-2960
642:0305-1048
218:base pair
202:guanosine
873:32412236
826:26902426
777:24469816
660:34520542
509:Archived
475:Archived
416:Archived
320:See also
289:testing.
286:in vitro
222:molecule
198:cytosine
181:Gameplay
172:switches
817:4833017
768:3926058
745:Bibcode
712:19 July
651:8499941
522:Science
194:adenine
117:folding
82:Website
61:English
879:
871:
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814:
775:
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658:
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331:Foldit
247:OpenTB
206:uracil
140:Foldit
98:Eterna
76:Puzzle
20:Eterna
877:S2CID
459:MSNBC
226:binds
214:bases
100:is a
869:PMID
861:ISSN
822:PMID
773:PMID
737:PNAS
714:2014
656:PMID
638:ISSN
602:2020
548:2016
295:PNAS
204:and
170:and
111:and
89:.org
67:Type
53:2010
947:RNA
853:doi
812:PMC
804:doi
800:428
763:PMC
753:doi
741:111
646:PMC
630:doi
187:RNA
121:RNA
119:of
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192:(
Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.