A deep learning approach to programmable RNA switches

Nat Commun. 2020 Oct 7;11(1):5057. doi: 10.1038/s41467-020-18677-1.

Abstract

Engineered RNA elements are programmable tools capable of detecting small molecules, proteins, and nucleic acids. Predicting the behavior of these synthetic biology components remains a challenge, a situation that could be addressed through enhanced pattern recognition from deep learning. Here, we investigate Deep Neural Networks (DNN) to predict toehold switch function as a canonical riboswitch model in synthetic biology. To facilitate DNN training, we synthesize and characterize in vivo a dataset of 91,534 toehold switches spanning 23 viral genomes and 906 human transcription factors. DNNs trained on nucleotide sequences outperform (R2 = 0.43-0.70) previous state-of-the-art thermodynamic and kinetic models (R2 = 0.04-0.15) and allow for human-understandable attention-visualizations (VIS4Map) to identify success and failure modes. This work shows that deep learning approaches can be used for functionality predictions and insight generation in RNA synthetic biology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Datasets as Topic
  • Deep Learning*
  • Genetic Engineering / methods*
  • Genome, Viral / genetics
  • Humans
  • Kinetics
  • Riboswitch / genetics*
  • Synthetic Biology / methods*
  • Thermodynamics
  • Transcription Factors / genetics

Substances

  • Riboswitch
  • Transcription Factors