RNA design rules from a massive open laboratory

Jeehyung Lee	Wipapat Kladwang	Minjae Lee	Daniel Cantu	Martin Azizyan	Hanjoo Kim	Alex Limpaecher	Sungroh Yoon	Adrien Treuille	Rhiju Das	EteRNA Participants

Proceedings of the National Academy of Sciences (2014)

Self-assembling RNA molecules present compelling substrates for the rational interrogation and control of living systems. However, imperfect in silico models—even at the secondary structure level—hinder the design of new RNAs that function properly when synthesized. Here, we present a unique and potentially general approach to such empirical problems: the Massive Open Laboratory. The EteRNA project connects 37,000 enthusiasts to RNA design puzzles through an online interface. Uniquely, EteRNA participants not only manipulate simulated molecules but also control a remote experimental pipeline for high-throughput RNA synthesis and structure mapping. We show herein that the EteRNA community leveraged dozens of cycles of continuous wet laboratory feedback to learn strategies for solving in vitro RNA design problems on which automated methods fail. The top strategies—including several previously unrecognized negative design rules—were distilled by machine learning into an algorithm, EteRNABot. Over a rigorous 1-y testing phase, both the EteRNA community and EteRNABot significantly outperformed prior algorithms in a dozen RNA secondary structure design tests, including the creation of dendrimer-like structures and scaffolds for small molecule sensors. These results show that an online community can carry out large-scale experiments, hypothesis generation, and algorithm design to create practical advances in empirical science.

Jeehyung Lee, Wipapat Kladwang, Minjae Lee, Daniel Cantu, Martin Azizyan, Hanjoo Kim, Alex Limpaecher, Sungroh Yoon, Adrien Treuille, Rhiju Das, EteRNA Participants (2014). RNA design rules from a massive open laboratory. Proceedings of the National Academy of Sciences, 111(6), 2122--2127.

@article{Lee:2014:RNA,
author = {Jeehyung Lee and Wipapat Kladwang and Minjae Lee and Daniel Cantu and Martin Azizyan and Hanjoo Kim and Alex Limpaecher and Sungroh Yoon and Adrien Treuille and Rhiju Das and EteRNA Participants},
day = {11},
doi = {10.1073/pnas.1313039111},
issn = {1091-6490},
journal = {Proceedings of the National Academy of Sciences},
keywords = {crowdsourcing},
month = feb,
number = {6},
pages = {2122--2127},
pmid = {24469816},
posted-at = {2014-02-26 13:23:43},
priority = {2},
publisher = {National Academy of Sciences},
title = {RNA design rules from a massive open laboratory},
url = {http://dx.doi.org/10.1073/pnas.1313039111},
volume = {111},
year = {2014}
}