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

TL;DR

This study employs advanced text mining and network analysis to identify key biomolecular events and potential biomarkers involved in high-altitude diseases, enhancing understanding of their molecular mechanisms.

Contribution

It introduces a novel biomolecular event extraction pipeline combining machine learning and graph kernels to analyze HAD-related literature and construct a comprehensive biomolecular network.

Findings

Identified over 150 biomolecular events related to HAD.

Constructed a network with 97 nodes and 153 edges highlighting key biomolecules.

Prioritized important biomarkers like EPO, VEGF, and HIF-1 alpha.

Abstract

High-altitude diseases (HAD), encompassing acute mountain sickness (AMS), high-altitude cerebral edema (HACE), and high-altitude pulmonary edema (HAPE), are triggered by hypobaric hypoxia at elevations above 2,500 meters. 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 7,847 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 (EPO) (0.0163), Vascular endothelial growth factor (VEGF) (0.0148), Hypoxia-inducible factor 1 (HIF-1) alpha (0.0136), Endothelial PAS Domain Protein 1 (EPAS1) and Angiotensin-Converting Enzyme (ACE) (0.0119), Egl nine homolog 1 (EGLN1), Endothelin 1 (ET-1), and 70 kilodalton heat shock protein (Hsp70)(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 high-altitude disease.