Expression Graph Network Framework for Biomarker Discovery

Authors

Yang Liu
Jason Huse
Kasthuri Kannan

Language

English

Publication Date

8-31-2025

Journal

Briefings in Bioinformatics

DOI

10.1093/bib/bbaf559

PMID

41139924

PMCID

PMC12554635

PubMedCentral® Posted Date

10-27-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Biomarker discovery for complex diseases, such as cancer, hinges on uncovering molecular signatures that capture intricate, interconnected relationships within biological data-a challenge that traditional statistical and machine learning methods often fail to meet due to the complexity of high-dimensional gene expression profiles. To overcome this, we introduce the expression graph network framework (EGNF). This cutting-edge graph-based approach integrates graph neural networks with network-based feature engineering to enhance the predictive identification of biomarkers. EGNF constructs biologically informed networks by combining gene expression data and clinical attributes within a graph database, utilizing hierarchical clustering to generate dynamic, patient-specific representations of molecular interactions. Leveraging graph learning techniques, including graph convolutional networks and graph attention networks, our framework identifies statistically significant and biologically relevant gene modules for classification. Validated across three independent datasets consisting of contrasting tumor types and clinical scenarios, EGNF consistently outperforms traditional machine learning models, achieving superior classification accuracy and interpretability. Notably, it delivers perfect separation between normal and tumor samples while excelling in nuanced tasks such as classifying disease progression and predicting treatment outcomes. This scalable, interpretable, and robust framework provides a powerful tool for biomarker discovery, with wide-ranging applications in precision medicine and the elucidation of disease mechanisms across diverse clinical contexts.

Keywords

Humans, Biomarkers, Tumor, Machine Learning, Neural Networks, Computer, Neoplasms, Computational Biology, Gene Expression Profiling, Gene Regulatory Networks, Biomarkers, biomarker, graph neural network, EGNF

Published Open-Access

yes

Recommended Citation

Yang Liu, Jason Huse, and Kasthuri Kannan, "Expression Graph Network Framework for Biomarker Discovery" (2025). Faculty, Staff and Student Publications. 5888.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5888