用玻尔兹曼机增强Transformer,让DNA分类模型更懂基因位点间的复杂互作。
A Boltzmann-machine-enhanced Transformer For DNA Sequence Classification
- 引入二元门控变量和能量函数,显式建模基因序列中位点间的结构化连接
- 通过变分推断与Gumbel-Softmax实现可微离散优化,提升结构可解释性
- 适合关注基因调控机制、高阶依赖关系的生物信息学研究者
DNA序列分类不仅需要高预测精度,还需揭示潜在的位点互作、组合调控及类似表型上位性的高阶依赖。尽管标准Transformer具备强全局建模能力,但其softmax注意力是连续、稠密且约束弱,更适合信息路由而非结构发现。本文提出一种玻尔兹曼机增强的Transformer用于DNA序列分类。在多头注意力基础上,引入结构化二元门控变量表示潜在查询-键连接,并以玻尔兹曼风格能量函数进行约束。查询-键相似性定义局部偏置项,可学习的成对交互捕捉边之间的协同与竞争,隐层单元建模更高阶组合依赖。由于精确的离散门图后验推断不可行,采用均值场变分推断估计边激活概率,并结合Gumbel-Softmax将连续概率逐步压缩为近离散门,同时保持端到端可微性。训练时联合优化分类损失与能量损失,促使模型在准确预测的同时偏好低能量、稳定且可解释的结构。进一步从能量函数与变分自由能推导出均值场不动点方程、Gumbel-Softmax松弛及最终联合目标。该框架统一了玻尔兹曼机、可微离散优化与Transformer在生物序列结构学习中的应用。
原文摘要 · Abstract (English)
DNA sequence classification requires not only high predictive accuracy but also the ability to uncover latent site interactions, combinatorial regulation, and epistasis-like higher-order dependencies. Although the standard Transformer provides strong global modeling capacity, its softmax attention is continuous, dense, and weakly constrained, making it better suited for information routing than explicit structure discovery. In this paper, we propose a Boltzmann-machine-enhanced Transformer for DNA sequence classification. Built on multi-head attention, the model introduces structured binary gating variables to represent latent query-key connections and constrains them with a Boltzmann-style energy function. Query-key similarity defines local bias terms, learnable pairwise interactions capture synergy and competition between edges, and latent hidden units model higher-order combinatorial dependencies. Since exact posterior inference over discrete gating graphs is intractable, we use mean-field variational inference to estimate edge activation probabilities and combine it with Gumbel-Softmax to progressively compress continuous probabilities into near-discrete gates while preserving end-to-end differentiability. During training, we jointly optimize classification and energy losses, encouraging the model to achieve accurate prediction while favoring low-energy, stable, and interpretable structures. We further derive the framework from the energy function and variational free energy to the mean-field fixed-point equations, Gumbel-Softmax relaxation, and the final joint objective. The proposed framework provides a unified view of integrating Boltzmann machines, differentiable discrete optimization, and Transformers for structured learning on biological sequences.
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