Fig. 1 | Scientific Reports

Fig. 1

From: Integrative bioinformatics frameworks for abdominal aortic aneurysm using GWAS meta-analysis, biological network construction, and structural modeling

Fig. 1

Workflow of integrative bioinformatics frameworks for abdominal aortic aneurysm (AAA). AAA genome-wide association study (GWAS) datasets were retrieved from the GWAS Catalog36 and subjected to meta-analysis using METAL43. Summary statistics from the meta-analysis were used to identify independent significant single nucleotide polymorphisms (SNPs) and expression quantitative trait loci (eQTLs) via FUMA29. Gene-set enrichment analysis was conducted using MAGMA47. Transcriptome-wide association study (TWAS) was performed using the FUSION pipeline49. Differentially expressed genes (DEGs) were determined based on genes that were significant in both the eQTL and TWAS analyses. An AAA-associated protein–protein interaction (PPI) network was constructed using the DEGs and interactome data from the STRING database51 and visualized with Cytoscape52. Key nodes in the network were identified based on high degree and betweenness centrality scores, calculated using the NetworkX package in Python53. Drug repurposing candidates were identified through screening drug–gene and drug–protein interaction databases, such as DrugBank57, Therapeutic Target Database (TTD)58, Comparative Toxicogenomics Databases (CTD)59, GeneCards60, and STITCH database61, and shortlisted drugs were further evaluated via computational structural modeling and molecular docking simulations using the HDOCK server71. The structural modeling results were visualized by the PDBsum website72, Accelrys Discovery Studio 3.0 (Accelrys Inc.)73, and the University of California at San Francisco (UCSF) Chimera package74.

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