AttnGen: Attention-Guided Saliency Learning for Interpretable Genomic Sequence Classification

Abstract

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.