@article{10.1172/jci.insight.93247, author = {Philip G. Murray AND Adam Stevens AND Chiara De Leonibus AND Ekaterina Koledova AND Pierre Chatelain AND Peter E. Clayton}, journal = {JCI Insight}, publisher = {The American Society for Clinical Investigation}, title = {Transcriptomics and machine learning predict diagnosis and severity of growth hormone deficiency}, year = {2018}, month = {4}, volume = {3}, url = {https://insight.jci.org/articles/view/93247}, abstract = {BACKGROUND. The effect of gene expression data on diagnosis remains limited. Here, we show how diagnosis and classification of growth hormone deficiency (GHD) can be achieved from a single blood sample using a combination of transcriptomics and random forest analysis. METHODS. Prepubertal treatment-naive children with GHD (n = 98) were enrolled from the PREDICT study, and controls (n = 26) were acquired from online data sets. Whole blood gene expression was correlated with peak growth hormone (GH) using rank regression and a random forest algorithm tested for prediction of the presence of GHD and in classification of GHD as severe (peak GH <4 μg/l) and nonsevere (peak ≥4 μg/l). Performance was assessed using area under the receiver operating characteristic curve (AUC-ROC). RESULTS. Rank regression identified 347 probe sets in which gene expression correlated with peak GH concentrations (r = ± 0.28, P < 0.01). These 347 probe sets yielded an AUC-ROC of 0.95 for prediction of GHD status versus controls and an AUC-ROC of 0.93 for prediction of GHD severity. CONCLUSION. This study demonstrates highly accurate diagnosis and disease classification for GHD using a combination of transcriptomics and random forest analysis. TRIAL REGISTRATION. NCT00256126 and NCT00699855. FUNDING. Merck and the National Institute for Health Research (CL-2012-06-005).}, number = {7}, doi = {10.1172/jci.insight.93247}, url = {https://doi.org/10.1172/jci.insight.93247}, }