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Elife. 2017 Feb 20;6. pii: e20214. doi: 10.7554/eLife.20214.

Blood transcriptome based biomarkers for human circadian phase.

Author information

1
Department of Microbial Sciences, School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom.
2
Bioinformatics Core Facility, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom.
3
Department of Computer Science, Faculty of Engineering and Physical Sciences, University of Surrey, Guildford, United Kingdom.
4
Surrey Sleep Research Centre, School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom.

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 R2 of predicted vs observed phase was 0.74, whereas for two samples taken 12 hr apart, R2 was 0.90. This blood transcriptome-based model enables assessment of circadian phase from a few samples.

KEYWORDS:

biomarker; chronotherapy; computational biology; human; machine learning; neurodegeneration; neuroscience; sleep disorders; systems biology; transcriptomics

PMID:
28218891
PMCID:
PMC5318160
DOI:
10.7554/eLife.20214
[Indexed for MEDLINE]
Free PMC Article

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