提出可微分的编码子均衡指标,让神经网络能优化异源表达序列。
Smooth $\%$MinMax: A Differentiable Relaxation for Codon Harmonization
- 用概率加权替代离散编码子使用,实现可微分建模。
- 在人源到大肠杆菌的翻译优化中逼近原指标效果。
- 适合做基于梯度的密码子序列生成与设计任务。
编码子和谐化旨在调整编码序列以适应异源表达,同时保持频繁与稀有编码子的天然分布模式,这些模式可能影响局部翻译动态和共翻译蛋白折叠。然而,广泛使用的和谐化指标如%MinMax基于离散编码子序列定义,难以与基于梯度的神经密码子设计兼容。本文提出Smooth %MinMax(%MinMax_(s)),作为传统硬性%MinMax(%MinMax_(h))的可微分松弛。%MinMax_(s)将离散的密码子使用值替换为概率加权的同义密码子使用值,并用Sigmoid门控插值替代硬性%Max/%Min分支。该形式保留了%MinMax_(h)的符号解释,同时支持对同义密码子概率和可学习参数的优化。在人源到大肠杆菌的密码子和谐化实验中,%MinMax_(s)能紧密逼近%MinMax_(h),并支持在同义密码子概率空间中的梯度驱动的分布匹配。结果表明,%MinMax_(s)是连接基于分布的密码子和谐化与神经同义序列设计之间的实用桥梁。
原文摘要 · Abstract (English)
Codon harmonization aims to adapt the coding sequences for heterologous expression while preserving the native-like patterns of frequent and rare codons that may influence local translation dynamics and co-translational protein folding. However, widely used harmonization metrics, such as $\%$MinMax, are defined on discrete codon sequences and are, therefore, not readily compatible with gradient-based neural codon design. Here, we introduce Smooth $\%$MinMax, denoted as $\%{\rm MinMax}_{(s)}$, a differentiable relaxation of the conventional hard $\%$MinMax metric, denoted as $\%{\rm MinMax}_{(h)}$. $\%{\rm MinMax}_{(s)}$ replaces the discrete codon-usage values with probability-weighted synonymous-codon usage values and replaces the hard $\%$Max/$\%$Min branch with a sigmoid-gated interpolation. This formulation preserves the signed interpretation of $\%{\rm MinMax}_{(h)}$, while enabling optimization with respect to the synonymous-codon probabilities and learnable parameters. In human-to-Escherichia coli codon harmonization experiments, $\%{\rm MinMax}_{(s)}$ closely approximates $\%{\rm MinMax}_{(h)}$ and supports gradient-based profile matching in synonymous-codon probability space. These results suggest $\%{\rm MinMax}_{(s)}$ as a practical bridge between profile-based codon harmonization and neural synonymous-sequence design.
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。