Transcriptomics and machine learning predict diagnosis and severity of growth hormone deficiency.

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).

SUBMITTER: Murray PG 

PROVIDER: S-EPMC5928867 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature