RT Journal Article
SR Electronic
T1 Deep learning of the regulatory grammar of yeast 5’ untranslated regions from 500,000 random sequences
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 137547
DO 10.1101/137547
A1 Josh Cuperus
A1 Benjamin Groves
A1 Anna Kuchina
A1 Alexander B. Rosenberg
A1 Nebojsa Jojic
A1 Stanley Fields
A1 Georg Seelig
YR 2017
UL http://biorxiv.org/content/early/2017/05/12/137547.abstract
AB 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.