通过编辑流实现可变长度DNA生成的推理阶段奖励控制。
LPDP: Inference-Time Reward Control for Variable-Length DNA Generation with Edit Flows

- 提出LPDP方法,在推理时动态优化可变长度DNA序列生成。
- 在增强子优化和外显子-内含子-外显子补全任务中显著提升生成质量。
- 适用于需要精细调控序列结构或剪接边界的生物序列设计场景。
我们研究了近期提出的编辑流在推理阶段奖励控制用于DNA序列生成的应用。与大多数在固定长度序列空间中操作的奖励引导式DNA生成框架不同,编辑流可通过生物学合理的插入、删除和替换操作生成可变长度的DNA。为此,我们提出局部扰动离散规划(LPDP),一种无需训练、关注中间状态与动作的局部重求解算子,用于推理阶段的可变长度DNA编辑动作生成器。具体而言,在每一步引导回溯中,LPDP评估单步根编辑,保留近最优的根带,并通过求解围绕子序列的有界局部离散规划重新排序每个保留的根。该局部规划利用编辑动作的类型化几何结构,聚焦于连贯的替换、插入或删除子图,并通过硬最大值备份或软对数求和指数(LSE)备份聚合局部延续。我们在两种情形下实例化LPDP:前端强化奖励倾斜用于增强子优化,早期编辑对建立全局调控序列结构至关重要;后端强化奖励倾斜用于外显子-内含子-外显子补全,晚期编辑精细调整剪接边界上下文。
原文摘要 · Abstract (English)
We study the application of recent Edit Flows for inference-time reward control for DNA sequence generation. Unlike most reward-guided DNA generation frameworks, which operate on fixed-length sequence spaces, Edit Flows have a potential to generate variable-length DNA through biologically plausible insertion, deletion, and substitution operations. In particular, we propose Local Perturbation Discrete Programming (LPDP), a training-free, intermediate-state and action-aware local re-solving operator for variable-length DNA edit-action generators at inference time. More specifically, at each guided rollout step, LPDP scores one-step root edits, retains a near-best root band, and re-ranks each retained root by solving a bounded local discrete program around its child sequence. This local program uses the typed geometry of edit actions to focus on coherent substitution, insertion, or deletion subgraphs, and aggregates local continuations with either a hard Max backup or a soft log-sum-exponential (LSE) backup. We instantiate LPDP in two regimes: front-loaded reward tilting for enhancer optimization, where early edits are critical for establishing global regulatory sequence structure, and back-loaded reward tilting for exon-intron-exon inpainting, where late edits fine-tune splice-boundary contexts.
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