Unraveling the Biomarker Prospects of High-Altitude Diseases: Insights from Biomolecular Event Network Constructed Using Text Mining

Abstract

High-altitude diseases (HAD), encompassing acute mountain sickness, high-altitude cerebral edema, and high-altitude pulmonary edema (HAPE), are triggered by hypobaric hypoxia at elevations above 2500 m. These conditions pose significant health risks, yet the molecular mechanisms remain insufficiently understood. In this study, we developed a biomolecular event extraction pipeline integrating supervised machine learning with feature-based and multiscale Laplacian graph kernels to analyze 7847 curated HAD-related abstracts from PubMed. We extracted over 150 unique biomolecular events—including gene expression, regulation, binding, and localization—and constructed a weighted, undirected biomolecular event network comprising 97 nodes and 153 edges. Using the PageRank algorithm, we prioritized key biomolecules based on their centrality within the event network. The top-ranked proteins included erythropoietin (0.0163), vascular endothelial growth factor (0.0148), hypoxia-inducible factor 1 alpha (0.0136), endothelial PAS domain protein 1 and angiotensin-converting enzyme (0.0119), and Egl nine homolog 1, endothelin 1, and 70-kilodalton heat shock protein (0.0118), all of which play crucial roles in oxygen sensing, vascular remodeling, erythropoiesis, and blood pressure regulation. Subnetwork analysis revealed three major functional clusters centered on hypoxia response, inflammation, and stress adaptation pathways. Our integrative approach demonstrates the utility of large-scale text mining and graph-based analysis to uncover mechanistic insights and prioritize potential biomarkers for HAD.

Received: 6 October 2025 | Revised: 7 January 2026 | Accepted: 6 February 2026

Conflicts of Interest

The authors declare that they have no conflicts of interest to this work.

Data Availability Statement

Data sharing is not applicable to this article as no new data were created or analyzed in this study

Author Contribution Statement

Balu Bhasuran: Conceptualization, Methodology, Software, Validation, Formal analysis, Investigation, Resources, Data curation, Writing - original draft, Writing - review & editing, Visualization. Sabenabanu Abdulkadhar: Methodology, Software, Validation, Formal analysis, Investigation, Resources, Data curation, Writing - original draft, Writing - review & editing, Visualization. Jeyakumar Natarajan: Conceptualization, Supervision, Project administration, Funding acquisition.