Compounds negatively correlated with T-ALL gene expression signature (P < .001)
| Rank . | Compound . | Target/function . | No. of instances . | Mean connectivity score . | Specificity . |
|---|---|---|---|---|---|
| 1 | Alvespimycin | HSP90 inhibitor | 12 | −0.456 | 0.000 |
| 2 | Wortmannin | PI3K inhibitor | 18 | −0.436 | 0.013 |
| 3 | Vorinostat | HDAC inhibitor | 12 | −0.344 | 0.248 |
| 4 | Geldanamycin | HSP90 inhibitor | 15 | −0.378 | 0.039 |
| 5 | Trifluoperazine | Phenothiazine | 16 | −0.325 | 0.048 |
| 6 | LY-294002 | PI3K inhibitor | 61 | −0.437 | 0.012 |
| 7 | Thioridazine | Phenothiazine | 20 | −0.423 | 0.065 |
| 8 | Sirolimus | mTOR inhibitor | 44 | −0.339 | 0.048 |
| 9 | Monorden | HSP90 inhibitor | 22 | −0.288 | 0.000 |
| 10 | Trichostatin A | HDAC inhibitor | 182 | −0.299 | 0.198 |
| 11 | Tanespimycin | HSP90 inhibitor | 62 | −0.349 | 0.076 |
| 12 | Fluphenazine | Phenothiazine | 18 | −0.331 | 0.017 |
| 13 | Puromycin | Antibiotic | 4 | −0.535 | 0.037 |
| 14 | Prochlorperazine | Phenothiazine | 16 | −0.322 | 0.047 |
| 15 | Cephaeline | Protein synthesis inhibitor | 5 | −0.384 | 0.066 |
| 16 | Anisomycin | MAPK/JNK inhibitor | 4 | −0.462 | 0.042 |
| 17 | Tonzonium bromide | Surfactant | 4 | −0.460 | 0.000 |
| 18 | 15-δ prostaglandin J2 | PPAR-γ agonist | 15 | −0.283 | 0.105 |
| 19 | Metixene | Anticholinergic | 4 | −0.393 | 0.000 |
| 20 | Nortriptyline | Tricyclic antidepressant | 4 | −0.439 | 0.007 |
| 21 | Emetine | Protein synthesis inhibitor | 4 | −0.466 | 0.053 |
| 22 | Desipramine | Tricyclic antidepressant | 4 | −0.401 | 0.000 |
| 23 | Terfenadine | Antihistamine | 3 | −0.534 | 0.028 |
| Rank . | Compound . | Target/function . | No. of instances . | Mean connectivity score . | Specificity . |
|---|---|---|---|---|---|
| 1 | Alvespimycin | HSP90 inhibitor | 12 | −0.456 | 0.000 |
| 2 | Wortmannin | PI3K inhibitor | 18 | −0.436 | 0.013 |
| 3 | Vorinostat | HDAC inhibitor | 12 | −0.344 | 0.248 |
| 4 | Geldanamycin | HSP90 inhibitor | 15 | −0.378 | 0.039 |
| 5 | Trifluoperazine | Phenothiazine | 16 | −0.325 | 0.048 |
| 6 | LY-294002 | PI3K inhibitor | 61 | −0.437 | 0.012 |
| 7 | Thioridazine | Phenothiazine | 20 | −0.423 | 0.065 |
| 8 | Sirolimus | mTOR inhibitor | 44 | −0.339 | 0.048 |
| 9 | Monorden | HSP90 inhibitor | 22 | −0.288 | 0.000 |
| 10 | Trichostatin A | HDAC inhibitor | 182 | −0.299 | 0.198 |
| 11 | Tanespimycin | HSP90 inhibitor | 62 | −0.349 | 0.076 |
| 12 | Fluphenazine | Phenothiazine | 18 | −0.331 | 0.017 |
| 13 | Puromycin | Antibiotic | 4 | −0.535 | 0.037 |
| 14 | Prochlorperazine | Phenothiazine | 16 | −0.322 | 0.047 |
| 15 | Cephaeline | Protein synthesis inhibitor | 5 | −0.384 | 0.066 |
| 16 | Anisomycin | MAPK/JNK inhibitor | 4 | −0.462 | 0.042 |
| 17 | Tonzonium bromide | Surfactant | 4 | −0.460 | 0.000 |
| 18 | 15-δ prostaglandin J2 | PPAR-γ agonist | 15 | −0.283 | 0.105 |
| 19 | Metixene | Anticholinergic | 4 | −0.393 | 0.000 |
| 20 | Nortriptyline | Tricyclic antidepressant | 4 | −0.439 | 0.007 |
| 21 | Emetine | Protein synthesis inhibitor | 4 | −0.466 | 0.053 |
| 22 | Desipramine | Tricyclic antidepressant | 4 | −0.401 | 0.000 |
| 23 | Terfenadine | Antihistamine | 3 | −0.534 | 0.028 |
Enrichment of both the up- and down-regulated genes from a given signature in the profiles of each treatment instance was estimated with a metric based on the Kolmogorov-Smirnov statistic and combined to produce a “connectivity score.” Instances were ranked by the descending order of connectivity scores; the frequency of an event can be taken as a P value. Specificity is defined as the frequency at which the enrichment of a set of instances in the ordered list of all instances in a given result is equaled or exceeded by the enrichment of that same set of instances in the set of results produced from queries executed with published, experimentally derived signatures.