INTERNATIONAL CONGRESS OF
CancerGenetics
Integrative Network and Variant-Effect Analysis Identifies Candidate Molecular Mediators of Photobiomodulation in Meningeal Lymphatic Endothelium
-
Najafi Mohammad,1 Fathabadi Amirhossein,2 Sazgarnia Ameneh,3 Rashidian Vaziri Mohammadreza,4 Shirokov Alexander,5 Sharif Samaneh,6,*
1. Medical Physics Research Center, Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
2. Medical Physics Research Center, Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
3. Medical Physics Research Center, Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
4. Department of Physics, Faculty of Sciences, Ferdowsi University, P. O. Box 9177948974, Mashhad, Iran
5. Department of Biology, Saratov State University, Astrakhanskaya Str. 83, 410012 Saratov, Russia
6. Medical Genetics Research Center, Mashhad University of Medical Sciences, P. O. Box 9177949224, Mashhad, Iran
- Introduction: Background: Meningeal lymphatic vessels (MLVs) regulate central nervous system fluid clearance and immune communication and have emerged as a potential target of photobiomodulation (PBM). Although PBM has been associated with enhanced lymphatic function, the molecular mediators connecting optical stimulation to lymphatic endothelial remodeling remain poorly defined. We therefore developed an integrative computational framework to prioritize candidate molecular mediators of PBM-associated MLV responses
- Methods: Methods: Genes associated with PBM response, redox signaling, and lymphatic endothelial function were integrated to construct a protein–protein interaction network using STRING. A PBM–lymphatic bridge interactome was reconstructed and characterized using degree, betweenness centrality, PageRank, and a network-based Bridge Score. Candidate prioritization combined normalized network topology with AlphaMissense-derived sequence-level information to generate an integrated Golden Score. Functional enrichment, restricted-background analysis, graph-theoretic node deletion, and annotation-density analysis were performed to evaluate biological context and potential network bias. Two independent murine lymphatic endothelial RNA-sequencing datasets were reanalyzed as complementary molecular evidence.
- Results: Results: The reconstructed bridge interactome contained 205 nodes and 4,074 interaction edges and showed strong local clustering with short path lengths. Network topology identified GAPDH and TP53 as the highest-ranking candidates, followed by TNF, AKT1, CYCS, and CTNNB1, whereas ACTB ranked seventh by topology alone. Integration of topology and AlphaMissense-derived information again prioritized GAPDH and TP53, with CTNNB1 and ACTB among the leading candidates. Functional enrichment identified processes related to wound healing, inflammatory signaling, vascular remodeling, and cell–cell junction organization, with enrichment of HIF-1, PI3K–AKT, focal adhesion, and tight-junction pathways. Restricting the enrichment background to the bridge interactome reduced nonspecific signals while preserving key endothelial and junctional associations. Node deletion identified GAPDH, ACTB, and TP53 as prominent structural bottlenecks. Transcriptomic reanalysis provided context-dependent molecular support without directly validating the proposed mechanism.
- Conclusion: Conclusion: An integrative network and sequence-level framework identified a focused set of candidate molecular mediators linking PBM-associated signaling with meningeal lymphatic endothelial remodeling. GAPDH, TP53, ACTB, and CTNNB1 emerged as particularly informative computational candidates. These findings provide a hypothesis-generating molecular framework for experimental investigation of PBM-responsive lymphatic and tumor-associated CNS biology.
- Keywords: Photobiomodulation; meningeal lymphatic vessels; transcriptomics; molecular prioritization; protein–
