# Deep learning models for predicting RNA degradation via dual crowdsourcing

arXiv: https://arxiv.org/abs/2110.07531 · HTML: https://mlsanity.com/paper/2110.07531/

## Key facts

- Cited by 8 papers in the map (data through 14 Oct 2026).
- Builds on 3 of its 31 references that are in the map.
- First posted on arXiv 14 Oct 2021.

## Builds on (most cited first, 3 of 3)

- [XGBoost: A Scalable Tree Boosting System](https://mlsanity.com/paper/1603.02754/) (2016)
- [Learning Phrase Representations using RNN Encoder-Decoder for Statistical Machine Translation](https://mlsanity.com/paper/1406.1078/) (2014)
- [Generating Sentences from a Continuous Space](https://mlsanity.com/paper/1511.06349/) (2015)

## Built on by (most cited first, 8 of 8)

- [HELM: Hierarchical Encoding for mRNA Language Modeling](https://mlsanity.com/paper/2410.12459/) (2024)
- [Beyond Sequence: Impact of Geometric Context for RNA Property Prediction](https://mlsanity.com/paper/2410.11933/) (2024)
- [BEACON: Benchmark for Comprehensive RNA Tasks and Language Models](https://mlsanity.com/paper/2406.10391/) (2024)
- [DualEquiNet: A Dual-Space Hierarchical Equivariant Network for Large Biomolecules](https://mlsanity.com/paper/2506.19862/) (2025)
- [Geometric Hyena Networks for Large-scale Equivariant Learning](https://mlsanity.com/paper/2505.22560/) (2025)
- [Equi-mRNA: Protein Translation Equivariant Encoding for mRNA Language Models](https://mlsanity.com/paper/2508.15103/) (2025)
- [HyperHELM: Hyperbolic Hierarchy Encoding for mRNA Language Modeling](https://mlsanity.com/paper/2509.24655/) (2025)
- [MultiMolecule: a modular ecosystem for biomolecular sequence-model workflows](https://mlsanity.com/paper/2606.16540/) (2026)

## Abstract (arXiv)

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.
