Figure 1
Overview of the bipartite graph-based method for drug repositioning.
Figure 2
Bipartite graph models for computing drug target similarity.
Table 1
Comparison of target similarities calculated by different methods.
| (d1, d2) | (d1, d3) | (d1, d4) | (d2, d3) | (d2, d4) | (d3, d4) | |
|---|---|---|---|---|---|---|
| |P(dx, dy)| | 1.00 | 0.00 | 0.00 | 1.00 | 1.00 | 1.00 |
| Pearson | 0.71 | 0.00 | 0.00 | 0.71 | 0.71 | 1.00 |
| R1(dx, dy) | 0.75 | 0.50 | 0.50 | 0.75 | 0.75 | 1.00 |
| R3(dx, dy) | 0.85 | 0.71 | 0.71 | 0.85 | 0.85 | 1.00 |
| R5(dx, dy) | 0.91 | 0.83 | 0.83 | 0.91 | 0.91 | 1.00 |
| R7(dx, dy) | 0.95 | 0.90 | 0.90 | 0.95 | 0.95 | 1.00 |
Figure 3
Scatter plots of (SIMchem.) and (SIMtarget.) computed by Pearson’s correlation.
Figure 4
Scatter plots of (SIMchem) and (SIMtarget) computed by our G2 method.
Figure 5
ROC curves of different drug-pairwise similarity strategies.
Table 2
Examples of repositioned drugs predicted by our method.
| Drug | Novel use | Similar drugs supporting this prediction | Evidence in clinical trial/literature |
|---|---|---|---|
| Fluoxetine | Alcoholism | Citalopram SIMchem = 0.66 SIMtarget = 0.53 (Common target P31645 (Sodium-dependent serotonin transporter)) | NCT00027378: Study fluoxetine (Prozac) versus a placebo in the treatment of adolescents with alcohol use disorder and major depression |
| Ramipril | Rheumatoid Arthritis | Enalapril SIMchem = 0.92 SIMtarget = 1 (Common target P12821 (Angiotensin-converting enzyme)) | NCT00273533: Evaluate that Ramipril improves vascular function and reduces markers of low-grade chronic inflammation and oxidative stress in patients with Rheumatoid Arthritis |
| Sildenafil | Brain Ischemia | Pentoxifylline SIMchem = 0.38 SIMtarget = 0.19 (Common target O76074 (cGMP-specific 3’,5’-cyclic phosphodiesterase)) | PMID 20436396: Study the therapeutic effect of sildenafil citrate on cerebral vasospasm in rat model |
| Carbidopa | Prostatic Neoplasms | Flutamide SIMchem = 0.42 SIMtarget = 0.33 (Interaction between Carbidopa’s target P20711(Aromatic-L-amino-acid decarboxylase) and Flutamide’s target P10275 (Androgen receptor)) | PMID 16895983: Treatment of nude mice containing prostate neuroendocrine cancer with carbidopa plus amiloride and flumazenil leading to significant reductions in tumor growth |
| Pimecrolimus | Graft-versus-host disease (GVHD) | Tacrolimus SIMchem = 0.89 SIMtarget = 0.78 (Common target P62942 (FK506-binding protein 1A); plus interaction between Pimecrolimus’s target P42345 (Serine/threonine-protein kinase mTOR) and the common target P62942) | PMID 20723118: Treatment of disfiguring chronic GVHD in a child with topical pimecrolimus: case report |