This article presents a Hierarchical Pathway-Masked Attention Autoencoder (H-PAAE), a biologically inspired representation-learning framework that enables explainable AI-guided cancer diagnosis. The model directly integrates the curated MSigDB Hallmark pathways, introducing pathway-constrained information flow and mechanistic interpretability through multi-level attention mechanisms. Based on TCGA RNA-seq data from 33 tumor types, H-PAAE compresses approximately 20,000 genes into a 128-dimensional latent space while preserving biologically meaningful structure. When used with XGBoost classification, H-PAAE delivers 92.37% test accuracy and 99.38% macro-AUROC with robust cross-validation results (92.5
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Computer Modeling in Engineering & Sciences 2026, 147(3): 29
Published: 30 June 2026
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