Systems Pharmacology Approach to Identifying Novel Drug Targets for Sickle Cell Disease Using Nigerian Patient-Derived Genomic and Proteomic Data

Background: Nigeria bears the world's highest burden of sickle cell disease (SCD), yet treatment options remain limited to hydroxyurea, voxelotor, and supportive care. Systems pharmacology, integrating genomics, proteomics, and network analysis, offers a powerful approach to discovering novel therapeutic targets within the unique genetic context of Nigerian SCD patients. This study employs a systems pharmacology approach to identify candidate drug targets using patient-derived omics data. Methods: Genomic DNA and plasma proteomics samples were collected from 200 SCD patients (HbSS) and 100 healthy HbAA controls recruited from haematology clinics in Lagos, Abuja, and Enugu. Whole exome sequencing and label-free quantitative proteomics were performed. Protein-protein interaction networks were constructed using STRING and Cytoscape. Differentially expressed proteins and variant-associated pathways were analysed for druggable target enrichment using the ChEMBL and DGIdb databases. Results: A total of 412 differentially expressed proteins were identified. Network analysis revealed 14 hub proteins significantly enriched in vaso-occlusion and oxidative stress pathways. Three candidate druggable targets, including HMOX1 and VCAM1 pathway modulators, were identified as novel versus existing SCD drug target annotations. Conclusion: Systems pharmacology applied to Nigerian SCD patient data reveals population-specific drug target opportunities. This framework advances precision pharmacology for the world's most affected SCD population. Keywords: sickle cell disease, systems pharmacology, genomics, proteomics, drug targets