Latent Diffusion Models for Controllable RNA Sequence Generation

• URL: http://arxiv.org/abs/2409.09828v2
• Date: Wed, 2 Oct 2024 16:42:46 GMT
• Title: Latent Diffusion Models for Controllable RNA Sequence Generation
• Authors: Kaixuan Huang, Yukang Yang, Kaidi Fu, Yanyi Chu, Le Cong, Mengdi Wang,
• Abstract summary: RNA is a key intermediary between DNA and protein, exhibiting high sequence diversity and complex three-dimensional structures. We develop a latent diffusion model for generating and optimizing discrete RNA sequences of variable lengths. Empirical results confirm that RNAdiffusion generates non-coding RNAs that align with natural distributions across various biological metrics.
• Score: 33.38594748558547
• License: http://creativecommons.org/licenses/by/4.0/
• Abstract: This work presents RNAdiffusion, a latent diffusion model for generating and optimizing discrete RNA sequences of variable lengths. RNA is a key intermediary between DNA and protein, exhibiting high sequence diversity and complex three-dimensional structures to support a wide range of functions. We utilize pretrained BERT-type models to encode raw RNA sequences into token-level, biologically meaningful representations. A Query Transformer is employed to compress such representations into a set of fixed-length latent vectors, with an autoregressive decoder trained to reconstruct RNA sequences from these latent variables. We then develop a continuous diffusion model within this latent space. To enable optimization, we integrate the gradients of reward models--surrogates for RNA functional properties--into the backward diffusion process, thereby generating RNAs with high reward scores. Empirical results confirm that RNAdiffusion generates non-coding RNAs that align with natural distributions across various biological metrics. Further, we fine-tune the diffusion model on mRNA 5' untranslated regions (5'-UTRs) and optimize sequences for high translation efficiencies. Our guided diffusion model effectively generates diverse 5'-UTRs with high Mean Ribosome Loading (MRL) and Translation Efficiency (TE), outperforming baselines in balancing rewards and structural stability trade-off. Our findings hold potential for advancing RNA sequence-function research and therapeutic RNA design.

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