Credit: (Printed image adapted from one provided by Hiroki Ueda.)

A new approach that uses gene-expression profiles to measure individual body time (BT) promises to make a big difference to the way we will administer drugs in the future.

Having access to an accurate clock or watch is pretty important — as anybody who has been late for an exam or an interview because of an unreliable timepiece can confirm! It can also be important to read the correct time from the body's circadian clock: administering drugs at an inappropriate BT can cause side-effects, whereas at the correct BT a drug's potency might be maximized and its toxicity minimized.

To address the lack of clinically applicable methods of BT detection, Hiroki Ueda and colleagues aimed to create a standard 'molecular timetable' of gene-expression profiles. First, they monitored genome-wide expression profiles from pooled liver samples, taken from BALB/c mice over a 2-day period, under either 12-hour cycles of light and dark, or constant dark conditions. The peak expression times for the 168 genes that had high circadian rhythmicity were distributed over a 24-hour period and did not differ between the two light/dark regimes, which indicated that they could provide a direct measure of the endogenous state of the circadian clock.

Next, the authors used a statistical approach that allowed the BT information to be extracted from the expression profiles of the time-indicating genes. The gradually changing expression profiles of night-indicating and day-indicating genes can be accurately modelled by the best-fitted cosine curve.

Their verification in independent samples indicated that this method could provide accurate estimates of BT. But how clinically useful is such a timetable? In mice, at least, the molecular timetable easily detected rhythm disorders in four Clock −/− mutants compared with wild-type mice. Moreover, given that circadian rhythmicity could also be detected in C3H mice, with the timetable that was calibrated in BALB/c mice, it seems this method is robust to changes in genetic background.

So, Ueda and colleagues might have provided a robust means of estimating BT from a single-point measurement: a long-held ambition for many clinicians. Of course, it is a long way from these experiments in inbred mouse strains to a routine clinical tool for humans, but given the number of genes in humans that show circadian expression patterns, there is certainly no obvious reason why the same approach would not be applicable.