Accurate Prediction of Circadian Clock to Aid Treatment of Diseases

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Highlights:

• First simple blood test to identify the precise internal time clock as compared to the external time has been developed
• The algorithm called TimeSignature is very accurate and efficient and estimates circadian time to within 2 h for the majority of samples
• The new test may be useful in the long run to guide personalized treatments

The body's precise internal time clock despite the time in the external world can now be taken accurately using only two blood draws. The simple blood test known as TimeSignature has been developed by Northwestern Medicine scientists that can tell physicians and researchers that even if it's 8 a.m. in the external world, it might be 6 a.m. in your body.

"This is a much more precise and sophisticated measurement than identifying whether you are a morning lark or a night owl," said lead author Rosemary Braun, assistant professor of preventive medicine (biostatistics) at Northwestern University Feinberg School of Medicine. "We can assess a person's biological clock to within 1.5 hours.

‘Circadian clock timing can be predicted accurately using a novel blood test called TimeSignature.’

The current test is accurate, easy to use and not as costly or laborious as earlier measurements. The paper is published in the journal PNAS.

Not everybody's internal biological clock is in sync with the external time. The internal clock or the circadian clock orchestrates processes in nearly every tissue and organ system in the body.

The synchronizations between the internal and external clocks become essential in the field of medicine. Misaligned circadian clocks can impact a range of diseases from heart disease to diabetes and Alzheimer's disease. The new test, when eventually available clinically, will provide doctors an accurate measurement of the internal body clock to guide medication dosing at the most effective time for a person's body.

"This is really an integral part of personalized medicine," said co-author Dr. Phyllis Zee, chief of sleep medicine in neurology at Feinberg and a Northwestern Medicine neurologist. "So many drugs have optimal times for dosing. Knowing what time it is in your body is critical to getting the most effective benefits. The best time for you to take the blood pressure drug or the chemotherapy or radiation may be different from somebody else."

TimeSignature - Blood Test to Determine the Internal Biological time clock

The researchers drew the subjects' blood every two hours and used the algorithm, TimeSignature to examine which genes are expressed higher or lower at certain times of the day. They also used gene expression data from four other studies.

A novel machine-learning method was developed to train a computer to predict the time of day using the patterns obtained in the gene expression measurements.

Out of about 20,000 genes measured, there were 40 gene expression markers that emerged with the strongest signal. Now that the machine-learning algorithm has been trained to "learn" the time of day as a function of gene expression in blood, it can be universally applied to yield accurate results in new gene expression data to make predictions that reflect the subjects' biological clock.

Disruption of the internal clock can predispose a person to a range of diseases. Preclinical research has linked circadian misalignment with obesity, heart disease, diabetes, depression, and asthma.

The scientists suggest that knowing how to measure the body's internal clock accurately can help in understanding if a disrupted clock has any connections with various diseases, and maybe, even predict who is going to get sick.

Overall, the scientists envision that they can improve health and treat disease by aligning people's circadian clocks that are out of sync with external time.

References:

1. SLEEP DRIVE AND YOUR BODY CLOCK
(https:sleepfoundation.org/sleep-topics/sleep-drive-and-your-body-clock)
2. Understanding your body's internal clock-or circadian rhythm-is the first step to better sleep
(https:sleep.org/articles/circadian-rhythm-body-clock/)

Source: Medindia

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