Repurposing Drugs for Infectious Diseases by Graph Convolutional Network with Sensitivity-Based Graph Reduction.

Computational systems biology employs computational algorithms and integrates diverse data sources, such as gene expression profiles, molecular interactions, and network modeling, to identify promising drug candidates through repurposing existing compounds in response to urgent healthcare needs. This study tackles the urgent need for rapid therapeutic development against emerging infectious diseases. We introduce a novel analytic expression for sensitivity analysis based on the Kronecker product and enhance model prediction performance using Graph Convolutional Networks (GCNs) with sensitivity-based graph reduction. Our algorithm refines prediction performance by leveraging sensitivity-based graph reduction. By integrating RNA-seq data, molecular interactions, and GCNs, we identify disease-related genes and pathways, construct heterogeneous graph models, and predict potential drugs. This approach involves novel analytical expressions that assess sensitivity to model loss, employing the Kronecker product approach. Subgraph analysis identifies nodes for removal, leading to a refined graph used for model retraining. This cost-effective pipeline focuses on computational methods for drug repurposing, targeting infectious diseases such as Zika virus and COVID-19 infection. Applied to these infections, our methodology integrates 659 proteins and 703 drugs for Zika virus, and 495 proteins and 468 drugs for COVID-19, along with their interactions derived from gene expression profiles. Top candidate drugs, such as Betamethasone phosphate and Bizelesin for Zika virus, and Chloroquine, Heparin Disaccharide, and Resveratrol for COVID-19, were validated through literature review or docking analysis. This scalable approach demonstrates promise in repurposing drugs for urgent healthcare challenges.