Crowdsourced RNA design discovers diverse, reversible, efficient, self-contained molecular switches.
Crowdsourced RNA design discovers diverse, reversible, efficient, self-contained molecular switches.
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众包RNA设计发现多样、可逆、高效、自包含的分子开关。
DOI：
10.1073/pnas.2112979119
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发表时间：
2022-05-03
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
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作者：
我们的手稿为开展分布式科学提供了一个范例。我们已经利用了一个在线RNA设计游戏Eterna，来挑战一个大型的RNA设计师社区，以创建不同的RNA传感器。RNA是一种有吸引力的，生物相容性的分子传感器的设计和实施基板。我们委托多元化的Eterna社区，包括分子设计爱好者的全球网络，提交数千到数万个“解决方案”来应对这些RNA传感器设计挑战。最重要的是，社区设计是在真实的世界中合成和实验测试的，使用的是基于重新设计的DNA测序仪的高通量生化分析方法。最好的球员产生的RNA传感器的设计接近热力学最佳。基于互联网的科学界承诺将分布式的、多样化的人类智慧应用于以前难以解决的科学问题。然而，目前的实现还不允许社区提出实验来大规模测试所有新兴的假设，或者修改假设以响应实验。我们报告了用于核酸分子表征的高通量方法，该方法使RNA传感器设计的大规模基于视频游戏的众包成为可能，然后进行高通量功能表征。对数千种众包RNA传感器设计的迭代设计测试产生了接近生物学最佳和可逆的RNA开关，其充当自包含的分子传感器，并将五种不同的小分子输入耦合到三种不同的蛋白质结合和荧光输出。这项工作为广泛分布的实验生物科学提供了一个范例。
Our manuscript presents a paradigm for carrying out distributed science. We have harnessed an online RNA design game, Eterna, to challenge a large community of RNA designers to create diverse RNA sensors. RNA is an attractive, biocompatible substrate for the design and implementation of molecular sensors. We tasked the diverse Eterna community, comprising a global network of molecular design enthusiasts, to submit thousands to tens of thousands of “solutions” to these RNA sensor design challenges. Crucially, community designs were synthesized and tested experimentally in the real world using high-throughput methods for biochemical assays built on repurposed DNA sequencers. The best player-generated designs for RNA sensors approached the thermodynamic optimum. Internet-based scientific communities promise a means to apply distributed, diverse human intelligence toward previously intractable scientific problems. However, current implementations have not allowed communities to propose experiments to test all emerging hypotheses at scale or to modify hypotheses in response to experiments. We report high-throughput methods for molecular characterization of nucleic acids that enable the large-scale video game–based crowdsourcing of RNA sensor design, followed by high-throughput functional characterization. Iterative design testing of thousands of crowdsourced RNA sensor designs produced near–thermodynamically optimal and reversible RNA switches that act as self-contained molecular sensors and couple five distinct small molecule inputs to three distinct protein binding and fluorogenic outputs. This work suggests a paradigm for widely distributed experimental bioscience.
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影响因子：
18.3
作者：
Deigan, Katherine E.;Ferre-D'Amare, Adrian R.
通讯作者：
Ferre-D'Amare, Adrian R.
DOI：
10.1126/science.1207339
发表时间：
2011-07-29
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Paige JS;Wu KY;Jaffrey SR
通讯作者：
Jaffrey SR
DOI：
10.1146/annurev-biodatasci-072018-021139
发表时间：
2019-01-01
期刊：
ANNUAL REVIEW OF BIOMEDICAL DATA SCIENCE, VOL 2, 2019
影响因子：
--
作者：
Das, Rhiju;Keep, Benjamin;Riedel-Kruse, Ingmar H.
通讯作者：
Riedel-Kruse, Ingmar H.
影响因子：
21.8
作者：
通讯作者：
--
影响因子：
1.8
作者：
HOFACKER, IL;FONTANA, W;SCHUSTER, P
通讯作者：
SCHUSTER, P