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Deep Learning Of The Regulatory Grammar Of Yeast 5′ Untranslated Regions From 500,000 Random Sequences

View ORCID ProfileJosh T. Cuperus, Benjamin Groves, Anna Kuchina, Alex B. Rosenberg, Nebojsa Jojic, Stanley Fields, Georg Seelig
doi: https://doi.org/10.1101/137547
Josh T. Cuperus
University of Washington;
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Benjamin Groves
University of Washington;
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Anna Kuchina
University of Washington;
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Alex B. Rosenberg
University of Washington;
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Nebojsa Jojic
Microsoft Research
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Stanley Fields
University of Washington;
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  • For correspondence: fields@uw.edu
Georg Seelig
University of Washington;
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Abstract

Our ability to predict protein expression from DNA sequence alone remains poor, reflecting our limited understanding of cis-regulatory grammar and hampering the design of engineered genes for synthetic biology applications. Here, we generate a model that predicts the translational efficiency of the 5′ untranslated region (UTR) of mRNAs in the yeast Saccharomyces cerevisiae. We constructed a library of half a million 50-nucleotide-long random 5′ UTRs and assayed their activity in a massively parallel growth selection experiment. The resulting data allow us to quantify the impact on translation of Kozak sequence composition, upstream open reading frames (uORFs) and secondary structure. We trained a convolutional neural network (CNN) on the random library and showed that it performs well at predicting the translational efficiency of both a held-out set of the random 5′ UTRs as well as native S. cerevisiae 5′ UTRs. The model additionally was used to computationally evolve highly translating 5′ UTRs. We confirmed experimentally that the great majority of the evolved sequences lead to higher translation rates than the starting sequences, demonstrating the predictive power of this model.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted May 19, 2017.
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Deep Learning Of The Regulatory Grammar Of Yeast 5′ Untranslated Regions From 500,000 Random Sequences
Josh T. Cuperus, Benjamin Groves, Anna Kuchina, Alex B. Rosenberg, Nebojsa Jojic, Stanley Fields, Georg Seelig
bioRxiv 137547; doi: https://doi.org/10.1101/137547
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Deep Learning Of The Regulatory Grammar Of Yeast 5′ Untranslated Regions From 500,000 Random Sequences
Josh T. Cuperus, Benjamin Groves, Anna Kuchina, Alex B. Rosenberg, Nebojsa Jojic, Stanley Fields, Georg Seelig
bioRxiv 137547; doi: https://doi.org/10.1101/137547

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