An Integrated Deep Learning Framework for Small-Sample Biomedical Data Classification: Explainable Graph Neural Networks with Data Augmentation for RNA sequencing Dataset

Applying deep learning models to RNA-Seq data poses substantial challenges, primarily due to the high dimensionality of the data and the limited sample sizes. To address these issues, this study introduces an advanced deep learning pipeline that integrates feature engineering with data augmentation. The engineering application focuses on biomedical engineering, specifically the classification of RNA-Seq datasets for disease diagnosis. The proposed framework was initially validated on synthetic datasets generated from Naive Bayes, where MLP-based augmentation yielded a notable improvement in predictive performance. Building on this foundation, we applied the approach to chromophobe renal cell carcinoma (KICH) RNA-Seq data from The Cancer Genome Atlas (TCGA). Following standard preprocessing steps normalization, transformation, and dimensionality reduction, the analysis concentrated on three main aspects: augmentation strategies, preprocessing methods, and explainable AI (XAI) techniques in relation to classification outcomes. Feature selection was performed through PCA, Boruta, and RF-based methods. Three augmentation strategies linear interpolation, SMOTE, and MixUp were evaluated. To maintain methodological rigor, augmentation was applied exclusively to the training set, while the test set was held out for unbiased evaluation. Within this framework, we conducted a comparative assessment of multiple deep learning architectures, including MLP, GNN, and the recently proposed Kolmogorov-Arnold networks (KAN). The GNN achieved the highest classification accuracy (99.47%) when trained with MixUp augmentation combined with RF feature selection, and achieved the best F1 score (0.9948). Consequently, the GNN-based XAI framework was applied to the RF dataset enriched with MixUp. XAI analyses identified the top 20 most influential genes, such as HNF4A, DACH2, MAPK15, and NAT2, which played the greatest role in classification, thereby confirming the biological plausibility of the model outputs. To further validate model robustness, cervical cancer and Alzheimer's RNA-Seq datasets were also tested, yielding consistent and reliable results. Overall, the findings highlight the value of incorporating data augmentation into deep learning models for RNA-Seq analysis, not only to improve predictive performance but also to enhance biological interpretability through explainable AI approaches.