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CHICAGO – Scientists from Northwestern Medicine have developed the first simple blood test to identify the precise internal clock of your body relative to the external time.
The test, TimeSignature – which requires only two blood tests – can tell doctors and researchers how much time is spent in your body despite the time spent in the outside world. For example, even if it's 8 am in the outside world, you may have 6 hours in your body.
"This is a much more accurate and sophisticated step than identifying whether you are a morning lark or a night owl," said lead author Rosemary Braun, assistant professor of preventive medicine (biostatistics) at Feinberg. School of Medicine, Northwestern University. "We can evaluate a person's biological clock in an hour and a half.
The test may reveal that it is 6 am in your body, but 8 am on the outside
"Various groups have tried to get an internal circadian test, but nothing has been as accurate or easy to use as TimeSignature," Braun said.
Previously, accurate measurements could only be obtained through an expensive and time-consuming process of taking samples every hour over several hours.
The article was published today, September 10, in the journal PNAS.
The processes in almost all tissues and organs of the body are orchestrated by an internal biological clock, which directs the circadian rhythm, such as the sleep-wake cycle. Some internal clocks of individuals are synchronized with external time, but others are out of sync and considered misaligned.
We can evaluate a person's biological clock in an hour and a half."
Assistant Professor of Preventive Medicine (Biostatistics), Feinberg School of Medicine, Northwestern University
The new test will for the first time allow researchers to easily examine the impact of poorly aligned circadian clocks on a range of diseases ranging from heart disease to diabetes and Alzheimer's disease. When the blood test eventually becomes clinically available, it will also provide physicians with a measure of the individual's internal biological clock to guide the dosage of the drug at the most effective time for its body.
The software and algorithm are freely available to other researchers so that they can evaluate the physiological time in a person's body. Northwestern has filed a patent on the blood test.
"It's really an integral part of personalized medicine," said Dr. Phyllis Zee, chief of sleep medicine in neurology at Feinberg and a neurologist at Northwestern Medicine. "So many drugs have optimal times for dosing. Knowing what time it is in your body is essential to getting the most effective benefits. The best time to take the medication for high blood pressure or chemotherapy or radiation therapy may be different than anyone else.
Zee is also the neurology professor Benjamin and Virginia T. Boshes.
The test measures 40 different markers of gene expression in the blood and can be taken at any time of the day, whether the patient has a good night's sleep or has spent the night with his baby. It is based on an algorithm developed by Braun and his colleagues by drawing subjects' blood every two hours and examining which genes were higher or lower at certain times of the day. Scientists also used gene expression data from studies conducted in four other centers.
Scientists then developed a new method of machine learning that was used to train a computer to predict the time of day based on the characteristics of these gene expression measures. Of about 20,000 genes measured, these 40 genes emerged with the strongest signal.
Doctors can dose drugs for maximum effectiveness based on circadian rhythm
"Timing is everything," said co-author of the study, Ravi Allada, a professor of neurobiology at Weinberg College of Arts and Sciences Northwestern. "We know that if your internal clock is disrupted, it can predispose you to various diseases. Virtually all tissues and organs are governed by the circadian rhythm.
"Before, we had no clinically feasible way to evaluate the clock in healthy people and people with diseases. Now, we can see if a disturbed clock is correlating with various diseases and, more importantly, whether it can predict who will get sick.
A link between circadian misalignment and diabetes, obesity, depression, heart disease, and asthma was identified during preclinical research by scientist Joe Bass, chief of endocrinology, the metabolism and molecular medicine in Feinberg.
Zee plans to improve health and treat diseases by aligning circadian clocks that are not synchronized with external time.
"Circadian timing is a modifiable risk factor for improving cognitive health, but if we can not measure it, it's hard to know if we've made the right diagnosis," Zee said. "Now we can measure it as a lipid level."
The document is entitled "A universal method for the robust detection of circadian status from gene expression".
The research was funded by the James S. McDonnell Foundation Scholar Award 220020394 and the Defense Advanced Research Projects Agency. (DARPA) Grant D15AP00027. Additional funding has been provided by the Northwestern Center for Circadian and Sleep Medicine.
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