用注意力引导的序列遮蔽,让基因组分类模型更准且可解释。
AttnGen: Attention-Guided Saliency Learning for Interpretable Genomic Sequence Classification

- 通过注意力机制动态识别重要核苷酸位置并逐步屏蔽低贡献区域。
- 在200碱基序列上准确率达96.73%,比传统CNN高0.9个百分点。
- 适合需要可解释性的基因组功能预测场景,如疾病相关突变分析。
深度神经网络在基因组序列分类中表现优异,但其预测与生物有意义的序列模式之间的关联仍具挑战性。本文提出AttnGen,一种将可解释性嵌入优化过程的注意力引导训练框架。AttnGen利用注意力机制计算核苷酸级重要性得分,并在训练中逐步抑制低贡献位置,促使模型聚焦于紧凑的信息区域,减少对噪声元素的依赖。我们在标准化的demo_human_or_worm基准上评估该方法,这是一个针对200碱基序列的二分类任务。在适度遮蔽条件下,AttnGen达到96.73%的验证准确率,优于传统CNN基线的95.83%,同时具备更快收敛性和更好训练稳定性。为检验学习到的重要性得分是否反映功能性信号,我们通过移除高显著性核苷酸进行扰动分析,结果显示在3,000个序列的测试集上准确率从96.9%降至接近随机水平,表明模型依赖相对少数信息位置。分析表明,遮蔽10–20%的位置在预测性能与可解释性之间取得最佳平衡。结果表明,注意力引导的遮蔽不仅提升分类性能,还重塑了模型对序列位置重要性的分布。尽管本研究聚焦短基因组序列,该方法可能推广至更复杂的可解释序列建模场景。
原文摘要 · Abstract (English)
Deep neural networks have achieved strong performance in genomic sequence classification; however, relating their predictions to biologically meaningful sequence patterns remains challenging. In this work, we present AttnGen, an attention-guided training framework that embeds interpretability directly into the optimization process. AttnGen computes nucleotide-level importance scores using an attention mechanism and progressively suppresses low-contribution positions during training. This encourages the model to focus its predictions on a compact set of informative regions while reducing reliance on noisy sequence elements. We evaluate AttnGen on the standardized demo_human_or_worm benchmark, a binary classification task over 200-nucleotide sequences. With moderate masking, AttnGen achieves a validation accuracy of 96.73%, outperforming a conventional CNN baseline with 95.83% accuracy, while also exhibiting faster convergence and improved training stability. To assess whether the learned importance scores reflect functionally relevant signal, we conduct perturbation-based analysis by removing high-saliency nucleotides. This causes accuracy to drop from 96.9% to near chance level on a 3,000-sequence evaluation set, indicating that the model relies on a relatively small subset of informative positions. Our analysis shows that masking 10--20% of positions provides the most favorable trade-off between predictive performance and interpretability. These results suggest that attention-guided masking not only improves classification performance but also reshapes how models distribute importance across sequence positions. Although this study focuses on short genomic sequences, the proposed approach may extend to more complex interpretable sequence modeling settings.
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