C9/TXR Systems Biology: Elucidating Drug Resistance Mechanisms
Challenge
The research team had identified that a subset of cancer cells developed resistance to taxane-based chemotherapy, mediated in part by C9 pathway activation. However, the precise molecular mechanisms and potential druggable targets within this resistance network remained poorly characterized. The team needed a comprehensive systems biology approach to elucidate the network topology and identify therapeutic entry points.
Approach
Science Habitat designed a multi-layer systems biology workflow integrating transcriptomics, protein interaction networks, and computational drug screening. We performed differential expression analysis on paired sensitive/resistant cell line data, constructed a protein-protein interaction network from the DEGs, and identified hub proteins driving resistance. Network-based target prioritization was followed by structure-based virtual screening against PubChem and ChEMBL compound libraries. Molecular docking (AutoDock Vina) and MD simulation (GROMACS) were used to validate top candidates, with ADMET profiling to filter for drug-likeness.
Tools & Pipeline
R / DESeq2,NetworkX, AutoDock Vina, GROMACS, SwissADME, pkCSM, PubChem,
Outcome
- Differential expression analysis results and pathway enrichment report
- PPI network with hub target identification
- Virtual screening results (top 20 candidates)
- Molecular docking scores and interaction diagrams
- MD simulation stability analysis (RMSD/RMSF plots)
- Publication-quality figures for all analysis steps
- Complete manuscript draft + peer review response