arXiv:2510.24736q-bio.QMcs.LG2025-10被引 1

用数学方法生成稳定有效的mRNA序列,提升疫苗与蛋白治疗设计效率

RNAGenScape: Property-Guided, Optimized Generation of mRNA Sequences with Manifold Langevin Dynamics

  • 基于真实数据学习序列潜空间,约束生成过程不偏离生物可行区域
  • 在三个真实数据集上使目标属性提升最高达148%,成功率提高30%
  • 适合生物医药研发人员,尤其关注mRNA药物设计与功能优化的团队

mRNA序列的属性优化在疫苗设计和蛋白替代疗法中至关重要,但受限于数据稀少、序列-功能关系复杂及生物可行序列空间狭窄。现有生成方法易偏离数据流形,产生无法折叠或翻译效率低的非功能性序列。本文提出RNAGenScape,一种基于流形Langevin动力学的属性引导生成框架,直接在真实数据学习到的流形上进行迭代优化。该框架包含三部分:(1) 联合训练的自编码器与属性预测器,构建属性有序的潜在流形;(2) 去噪自编码器,将更新投影回流形;(3) 属性引导的Langevin动力学,沿流形执行优化。在覆盖两个数量级规模的三个真实mRNA数据集上,RNAGenScape将中位属性增益提升最高达148%,成功率提升最高30%,同时保证生成序列的生物可行性,推理效率与现有生成方法相当。

原文摘要 · Abstract (English)

Generating property-optimized mRNA sequences is central to applications such as vaccine design and protein replacement therapy, but remains challenging due to limited data, complex sequence-function relationships, and the narrow space of biologically viable sequences. Generative methods that drift away from the data manifold can yield sequences that fail to fold, translate poorly, or are otherwise nonfunctional. We present RNAGenScape, a property-guided manifold Langevin dynamics framework for mRNA sequence generation that operates directly on a learned manifold of real data. By performing iterative local optimization constrained to this manifold, RNAGenScape preserves biological viability, accesses reliable guidance, and avoids excursions into nonfunctional regions of the ambient sequence space. The framework integrates three components: (1) an autoencoder jointly trained with a property predictor to learn a property-organized latent manifold, (2) a denoising autoencoder that projects updates back onto the manifold, and (3) a property-guided Langevin dynamics procedure that performs optimization along the manifold. Across three real-world mRNA datasets spanning two orders of magnitude in size, RNAGenScape increases median property gain by up to 148% and success rate by up to 30% while ensuring biological viability of generated sequences, and achieves competitive inference efficiency relative to existing generative approaches.

mRNA生成流形优化生物序列设计

Thank you to arXiv for use of its open access interoperability. PaperDance 不是 arXiv 官方产品;中文卡片由大模型生成,请以原文为准。