3 research outputs found
Deep learning models for predicting RNA degradation via dual crowdsourcing
Medicines based on messenger RNA (mRNA) hold immense potential, as evidenced by their rapid deployment as COVID-19 vaccines. However, worldwide distribution of mRNA molecules has been limited by their thermostability, which is fundamentally limited by the intrinsic instability of RNA molecules to a chemical degradation reaction called in-line hydrolysis. Predicting the degradation of an RNA molecule is a key task in designing more stable RNA-based therapeutics. Here, we describe a crowdsourced machine learning competition (‘Stanford OpenVaccine’) on Kaggle, involving single-nucleotide resolution measurements on 6,043 diverse 102–130-nucleotide RNA constructs that were themselves solicited through crowdsourcing on the RNA design platform Eterna. The entire experiment was completed in less than 6 months, and 41% of nucleotide-level predictions from the winning model were within experimental error of the ground truth measurement. Furthermore, these models generalized to blindly predicting orthogonal degradation data on much longer mRNA molecules (504–1,588 nucleotides) with improved accuracy compared with previously published models. These results indicate that such models can represent in-line hydrolysis with excellent accuracy, supporting their use for designing stabilized messenger RNAs. The integration of two crowdsourcing platforms, one for dataset creation and another for machine learning, may be fruitful for other urgent problems that demand scientific discovery on rapid timescales
Deep learning models for predicting RNA degradation via dual crowdsourcing
Messenger RNA-based medicines hold immense potential, as evidenced by their
rapid deployment as COVID-19 vaccines. However, worldwide distribution of mRNA
molecules has been limited by their thermostability, which is fundamentally
limited by the intrinsic instability of RNA molecules to a chemical degradation
reaction called in-line hydrolysis. Predicting the degradation of an RNA
molecule is a key task in designing more stable RNA-based therapeutics. Here,
we describe a crowdsourced machine learning competition ("Stanford
OpenVaccine") on Kaggle, involving single-nucleotide resolution measurements on
6043 102-130-nucleotide diverse RNA constructs that were themselves solicited
through crowdsourcing on the RNA design platform Eterna. The entire experiment
was completed in less than 6 months, and 41% of nucleotide-level predictions
from the winning model were within experimental error of the ground truth
measurement. Furthermore, these models generalized to blindly predicting
orthogonal degradation data on much longer mRNA molecules (504-1588
nucleotides) with improved accuracy compared to previously published models.
Top teams integrated natural language processing architectures and data
augmentation techniques with predictions from previous dynamic programming
models for RNA secondary structure. These results indicate that such models are
capable of representing in-line hydrolysis with excellent accuracy, supporting
their use for designing stabilized messenger RNAs. The integration of two
crowdsourcing platforms, one for data set creation and another for machine
learning, may be fruitful for other urgent problems that demand scientific
discovery on rapid timescales