Generative Artificial Intelligence vs. Transformer and Benchmarking Against Deep/Machine Learning: Classification and Scientific Validation of Heart Failure Patients Using Women’s Transcriptomic Gene Data

Backgrounds: Accurate early classification of heart failure (HF) in women is challenging due to sex-specific gene expression and disease patterns, which traditional models overlook. We propose a generative artificial intelligence (GenAI)-based model for the classification of HF patients using acute myocardial infarction (AMI) gene expression data. Objectives: This study aims to design and scientifically validate a novel GenAI framework, benchmarking it against transformer, deep learning (DL), and machine learning (ML) architectures for robust HF classification using women’s transcriptomic data. Methods: Total 26 models designed: A novel wBio-GenAI model, two transformers (Xmers): token diffusion gene (wTDG-Xmer) and neurotopology (wNT-Xmer), 19 deep learning models which include convolutional neural network (CNN)-, long short-term memory (LSTM)- and extended LSTM (xLSTM)-based models, and four ML. The models applied differential expression analysis (DEA) which identifies differentially expressed genes (DEGs) from the public women’s microarray GSE57345 samples. Quality control was conducted. The GenAI system was scientifically validated, benchmarked, and statistically tested for reliability. Results: The wBio-GenAI achieved an accuracy of 98.21% and an area-under-the-curve (AUC) of 0.99. The wBio-GenAI is better than the mean of two Xmers by 4.67%, the mean of 19 DLs by 5.16%, and the mean of four MLs by 15.07%. The proposed model meets the regulatory requirements of having a difference < 10% between seen and unseen paradigms. Conclusions: The wBio-GenAI architecture captures the complex transcriptomic patterns, improving HF classification in women and advancing women-specific precision cardiovascular care.