Blood transcriptome based biomarkers for human circadian phase.
other · Level V
Where this comes from
- Record sourced from PubMed, PMID 28218891.
- Also identified by DOI 10.7554/eLife.20214 and PMC identifier 5318160.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Diagnosis and treatment of circadian rhythm sleep-wake disorders both require assessment of circadian phase of the brain's circadian pacemaker. The gold-standard univariate method is based on collection of a 24-hr time series of plasma melatonin, a suprachiasmatic nucleus-driven pineal hormone. We developed and validated a multivariate whole-blood mRNA-based predictor of melatonin phase which requires few samples. Transcriptome data were collected under normal, sleep-deprivation and abnormal sleep-timing conditions to assess robustness of the predictor. Partial least square regression (PLSR), applied to the transcriptome, identified a set of 100 biomarkers primarily related to glucocorticoid signaling and immune function. Validation showed that PLSR-based predictors outperform published blood-derived circadian phase predictors. When given one sample as input, the R<sup>2</sup> of predicted vs observed phase was 0.74, whereas for two samples taken 12 hr apart, R<sup>2</sup> was 0.90. This blood transcriptome-based model enables assessment of circadian phase from a few samples.
Medical subject headings
- Biomarkers
- Circadian Rhythm
- Gene Expression Profiling
- Melatonin