GEMDiff: a diffusion workflow bridges between normal and tumor gene expression states: a breast cancer case study.

Abstract

Breast cancer remains a significant global health challenge due to its complexity, which arises from multiple genetic and epigenetic mutations that originate in normal breast tissue. Traditional machine learning models often fall short in addressing the intricate gene interactions that complicate drug design and treatment strategies. In contrast, our study introduces GEMDiff, a novel computational workflow leveraging a diffusion model to bridge the gene expression states between normal and tumor conditions. GEMDiff augments RNAseq data and simulates perturbation transformations between normal and tumor gene states, enhancing biomarker identification. GEMDiff can handle large-scale gene expression data without succumbing to the scalability and stability issues that plague other generative models. By avoiding the need for task-specific hyper-parameter tuning and specific loss functions, GEMDiff can be generalized across various tasks, making it a robust tool for gene expression analysis. The model's ability to augment RNA-seq data and simulate gene perturbations provides a valuable tool for researchers. This capability can be used to generate synthetic data for training other machine learning models, thereby addressing the issue of limited biological data and enhancing the performance of predictive models. The effectiveness of GEMDiff is demonstrated through a case study using breast mRNA gene expression data, identifying 307 core genes involved in the transition from a breast tumor to a normal gene expression state. GEMDiff is open source and available at https://github.com/xai990/GEMDiff.git under the MIT license.