Table 3. Validation of the predictive genes from the current exploratory study against previous studies examining GC response in cellular systems.
| Study title | GEO # | PMID | N | AUC (95% CI) |
OOB* AUC† |
OOB* error rate‡ (%) |
|---|---|---|---|---|---|---|
| Dexamethasone effect on epidermal keratinocytes in vitro | GSE26487 | 17095510 (Stojadinovic et al., 2007) | 20 | 0.70 (0.51–0.89) |
0.80 | 30 |
| Dexamethasone effect on GC-resistant and -sensitive lymphoblastic leukemia cell lines | GSE22152 | 21092265 (Carlet et al., 2010) | 24 | 0.71 (0.52–0.90) |
0.78 | 29 |
| In vivo GC effect on non-leukemic peripheral blood lymphocytes | GSE22779 | 21092265 (Carlet et al., 2010) | 16 | 0.88 (0.63–1.0) |
0.96 | 6 |
| Osteosarcoma cell line response to activation of specific GC receptor alpha isoforms | GSE6711 | 17682054 (Lu et al., 2007) 22174376 (Jewell et al., 2012) |
60 | 0.96 (0.89–1.0) |
0.99 | 3 |
| GC effect on lens epithelial cells | GSE3040 | 16319822 (Gupta et al., 2005) | 12 | 0.83 (0.63–1.0) |
0.72 | 17 |
*OOB data, the bootstrapping approach of Random Forest, ensures that every tree is built using ~63% of the available data, leaving ~ 37% that can be used for a validation test.
†AUC up to 0.96 demonstrates a high probability of correctly classifying a randomly selected sample from each study.
‡OOB error rate = prediction error using the OOB validation data.
The gene set that classified both PBMC and adipose tissue transcriptomes in relation to GC exposure with fold change in the same direction (see Figure 4B – 59 genes) was validated by further testing in five other publicly available studies of GC action in cellular systems.
AUC: area under the curve of the receiver operating characteristic; CI: confidence interval; GC: glucocorticoid; GEO: Gene Expression Omnibus; GEO #: study number deposited with GEO; N: study number size; OOB: out-of-bag; PBMC: peripheral blood mononuclear cell; PMID: PubMed ID number of the manuscript describing the data.