提出新方法实现可控制的生物序列生成,支持从DNA到蛋白质的高效设计。
Gumbel-Softmax Flow Matching with Straight-Through Guidance for Controllable Biological Sequence Generation
- 基于时变温度的Gumbel-Softmax插值构建连续单纯形上的流匹配框架。
- 在高维单纯形上实现高质量、多样化的序列生成,支持条件生成与无训练引导。
- 适用于罕见病治疗肽段设计等场景,无需额外训练即可使用预训练分类器引导。
连续单纯形上的流匹配已成为DNA序列设计的有前景方法,但在扩展至肽和蛋白生成所需的更高维单纯形时面临挑战。本文提出基于新型时变温度Gumbel-Softmax插值的Gumbel-Softmax流匹配与得分匹配框架,通过参数化速度场将平滑类别分布映射至单纯形单一顶点的集中分布。同时提出基于梯度回归的得分匹配方法。该框架支持高质量、多样化的序列生成,并可高效扩展至高维单纯形。为实现无需训练的引导,提出直通引导流(STGFlow),利用直通估计器引导无条件速度场向最优顶点逼近,仅需预训练分类器即可实现推理阶段高效引导,兼容任意离散流方法。在条件性DNA启动子设计、仅序列蛋白生成及罕见病靶向肽段设计任务中均达到当前最佳性能。
原文摘要 · Abstract (English)
Flow matching in the continuous simplex has emerged as a promising strategy for DNA sequence design, but struggles to scale to higher simplex dimensions required for peptide and protein generation. We introduce Gumbel-Softmax Flow and Score Matching, a generative framework on the simplex based on a novel Gumbel-Softmax interpolant with a time-dependent temperature. Using this interpolant, we introduce Gumbel-Softmax Flow Matching by deriving a parameterized velocity field that transports from smooth categorical distributions to distributions concentrated at a single vertex of the simplex. We alternatively present Gumbel-Softmax Score Matching which learns to regress the gradient of the probability density. Our framework enables high-quality, diverse generation and scales efficiently to higher-dimensional simplices. To enable training-free guidance, we propose Straight-Through Guided Flows (STGFlow), a classifier-based guidance method that leverages straight-through estimators to steer the unconditional velocity field toward optimal vertices of the simplex. STGFlow enables efficient inference-time guidance using classifiers pre-trained on clean sequences, and can be used with any discrete flow method. Together, these components form a robust framework for controllable de novo sequence generation. We demonstrate state-of-the-art performance in conditional DNA promoter design, sequence-only protein generation, and target-binding peptide design for rare disease treatment.
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。