Normalized coefficient of variation (nCV): a method to evaluate circadian clock robustness in population scale data.

Area of Science:

• Chronobiology
• Cancer Biology
• Bioinformatics

Background:

• Circadian rhythms are regulated by robust oscillations of clock genes.
• Relative amplitude (rAMP) quantifies oscillation robustness but requires time-labeled samples.
• A method to assess clock robustness in unlabeled human samples is needed.

Purpose of the Study:

• To develop a novel method for estimating circadian clock gene oscillation robustness in unlabeled human samples.
• To investigate the utility of normalized coefficient of variation (nCV) as a measure of clock robustness.
• To explore the potential of clock robustness as a therapeutic target in cancer.

Main Methods:

• Calculated normalized coefficient of variation (nCV) for 10 clock genes.
• Correlated nCV with normalized relative amplitude (rAMP) across datasets.
• Compared mean nCV of clock genes in tumor versus nontumor human samples.

Main Results:

• nCV of clock genes is linearly correlated with normalized rAMP, independent of time labels.
• Mean nCV of clock genes is consistently decreased in tumors compared to nontumors.
• nCV provides a simple and effective measure of clock robustness in population-level data.

Conclusions:

• Normalized coefficient of variation (nCV) offers a viable method for assessing circadian clock robustness in unlabeled samples.
• Reduced clock gene oscillation robustness, indicated by decreased nCV, is a feature of tumors.
• Enhancing circadian clock robustness presents a potential new therapeutic strategy for cancer treatment.