Integrative Rare Disease Biomedical Profile based Network Supporting Drug Repurposing, a case study of Glioblastoma

Abstract

Background Glioblastoma (GBM) is the most aggressive and common malignant primary brain tumor; however, treatment remains a significant challenge. This study aims to identify drug repurposing candidates for GBM by developing an integrative rare disease profile network containing heterogeneous types of biomedical data.Methods We developed a Glioblastoma-based Biomedical Profile Network (GBPN) by extracting and integrating biomedical information pertinent to GBM-related diseases from the NCATS GARD Knowledge Graph (NGKG). We further clustered the GBPN based on modularity classes which resulted in multiple focused subgraphs, named mc_GBPN. We then identified high-influence nodes by performing network analysis over the mc_GBPN and validated those nodes that could be potential drug repositioning candidates for GBM.Results We developed the GBPN with 1,466 nodes and 107,423 edges and consequently the mc_GBPN with forty-one modularity classes. A list of the ten most influential nodes were identified from the mc_GBPN. These notably include Riluzole, stem cell therapy, cannabidiol, and VK-0214, with proven evidence for treating GBM.Conclusion Our GBM-targeted network analysis allowed us to effectively identify potential candidates for drug repurposing. This could lead to less invasive treatments for glioblastoma while significantly reducing research costs by shortening the drug development timeline. Furthermore, this workflow can be extended to other disease areas.

The Vital Role Played by Deferiprone in the Transition of Thalassaemia from a Fatal to a Chronic Disease and Challenges in Its Repurposing for Use in Non-Iron-Loaded Diseases

“…These categories include millions of patients with cancer and neurodegenerative, infectious, and other diseases [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 ]. Similarly, drug repurposing is very important for many categories of patients with orphan diseases, particularly the millions of patients in developing countries, where health resources are scarce [ 10 , 11 , 12 ].…”

“…These categories include millions of patients with cancer and neurodegenerative, infectious, and other diseases [1][2][3][4][5][6][7][8][9]. Similarly, drug repurposing is very important for many categories of patients with orphan diseases, particularly the millions of patients in developing countries, where health resources are scarce [10][11][12]. Some of the major categories of diseases affecting humans are those related to the abnormal metabolism of iron, an essential metal required by all cells of the body and also by microbes and cancer cells.…”