# Harnessing Hypergraphs in Geometric Deep Learning for 3D RNA Inverse Folding

arXiv: https://arxiv.org/abs/2512.03592 · HTML: https://mlsanity.com/paper/2512.03592/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 14 of its 54 references that are in the map.
- First posted on arXiv 3 Dec 2025.

## Builds on (most cited first, 14 of 14)

- [PyTorch: An Imperative Style, High-Performance Deep Learning Library](https://mlsanity.com/paper/1912.01703/) (2019)
- [Hypergraph Neural Networks](https://mlsanity.com/paper/1809.09401/) (2018)
- [Learning from Protein Structure with Geometric Vector Perceptrons](https://mlsanity.com/paper/2009.01411/) (2020)
- [GroupNet: Multiscale Hypergraph Neural Networks for Trajectory Prediction with Relational Reasoning](https://mlsanity.com/paper/2204.08770/) (2022)
- [gRNAde: Geometric Deep Learning for 3D RNA inverse design](https://mlsanity.com/paper/2305.14749/) (2023)
- [Prototype-Based Image Prompting for Weakly Supervised Histopathological Image Segmentation](https://mlsanity.com/paper/2503.12068/) (2025)
- [RNAFlow: RNA Structure & Sequence Design via Inverse Folding-Based Flow Matching](https://mlsanity.com/paper/2405.18768/) (2024)
- [Multimodal Cancer Survival Analysis via Hypergraph Learning with Cross-Modality Rebalance](https://mlsanity.com/paper/2505.11997/) (2025)
- [Towards Joint Sequence-Structure Generation of Nucleic Acid and Protein Complexes with SE(3)-Discrete Diffusion](https://mlsanity.com/paper/2401.06151/) (2023)
- [Hypergraph Tversky-Aware Domain Incremental Learning for Brain Tumor Segmentation with Missing Modalities](https://mlsanity.com/paper/2505.16809/) (2025)
- [Spatially Gene Expression Prediction using Dual-Scale Contrastive Learning](https://mlsanity.com/paper/2506.23827/) (2025)
- [Boundary-Guided Learning for Gene Expression Prediction in Spatial Transcriptomics](https://mlsanity.com/paper/2412.04072/) (2024)
- [RNA-FrameFlow: Flow Matching for de novo 3D RNA Backbone Design](https://mlsanity.com/paper/2406.13839/) (2024)
- [Inhomogeneous Social Recommendation with Hypergraph Convolutional Networks](https://mlsanity.com/paper/2111.03344/) (2021)

## Abstract (arXiv)

The RNA inverse folding problem, a key challenge in RNA design, involves identifying nucleotide sequences that can fold into desired secondary structures, which are critical for ensuring molecular stability and function. The inherent complexity of this task stems from the intricate relationship between sequence and structure, making it particularly challenging. In this paper, we propose a framework, named HyperRNA, a generative model with an encoder-decoder architecture that leverages hypergraphs to design RNA sequences. Specifically, our HyperRNA model consists of three main components: preprocessing, encoding and decoding. In the preprocessing stage, graph structures are constructed by extracting the atom coordinates of RNA backbone based on 3-bead coarse-grained representation. The encoding stage processes these graphs, capturing higher order dependencies and complex biomolecular interactions using an attention embedding module and a hypergraph-based encoder. Finally, the decoding stage generates the RNA sequence in an autoregressive manner. We conducted quantitative and qualitative experiments on the PDBBind and RNAsolo datasets to evaluate the inverse folding task for RNA sequence generation and RNA-protein complex sequence generation. The experimental results demonstrate that HyperRNA not only outperforms existing RNA design methods but also highlights the potential of leveraging hypergraphs in RNA engineering.