High-accuracy determination of internal circadian time from a single blood sample

Abstract

This study was supported by the Bundesministerium für Bildung und Forschung, Germany (FKZ: 13N13160 and 13N13162) and Intellux GmbH, Germany.

The importance of determining circadian parameters in pharmacological studies

“…While the authors used the most comprehensive multi‐organ circadian data set available at the time (Zhang et al, ) as the training set, the method can be applied to any data set and has recently been used in the analysis of the core clock in cancer models (El‐Athman et al, ). Similar models have further been developed such as BodyTime or TimeSignature (Braun et al, ; Wittenbrink et al, ). These methods can be used to determine the chronotype of patients and can aid in both stratifying patients and optimizing treatment times based on circadian clock phenotypes (Ballesta et al, ; El‐Athman & Relógio, ; Zhang et al, ).…”

Systems approach reveals photosensitivity and PER 2 level as determinants of clock‐modulator efficacy

“…This adaptive chronotherapeutics requires a precise quantification of the drug‐induced circadian phase shift in daily life. Recently, to overcome the insufficient accuracy of actigraphy and labor‐intensive measurement of dim light melatonin onset (Duffy & Dijk, ; Ancoli‐Israel et al , ), various methods have been developed, which are based on the metabolite timetable (Kasukawa et al , ), one‐time phase estimation (Wittenbrink et al , ), or sleep‐tracking using mobile phone (Walch et al , ). With these advances, the adaptive chronotherapeutics could play a critical role in incorporating biomarker data and providing real‐time patient‐tailored chronotherapy via smart devices (i.e., digital medicine) (Elenko et al , ).…”

The importance of being rhythmic: Living in harmony with your body clocks

“…Those protocols are based on "constant routine" which imposes constant light, temperature, posture, evenly distributed food intake and usually sleep deprivation for the duration of 24 hours or more, and "forced desynchrony", discussed in the previous chapter. 81,176 Considerably less invasive methods for studying human clocks in vivo comprise questionnaires, notably the Munich Chronotype Questionnaire, 177,178 along with simple measurements that can be conducted in the home environment of the participant, such as activity rhythm by actigraphy, 179 thoracic skin temperature measurement using contact thermometry, 180 or serial urine and saliva sampling followed by melatonin assessment. Additionally, a lack of protocol standardization limits the direct comparison of the outcomes between the different studies.…”

“…Limitations of this approach are the high invasiveness for the participant in case of serial tissue biopsies, insufficient time resolution and exclusion of repetitive biopsies for most human tissues. To overcome these challenges, recent attempts for "reconstructing" an individual clockwork have been made based on a single controlled blood test, 176 or on previously collected tissue biopsies. 81 This methodology holds great promise for minimizing the need of tissue sampling, thus rendering the sample collection significantly less invasive.…”

“…The precision of clockwork evaluation based on a single measurement may still represent a challenge, although advanced mathematical algorithms bear a tremendous potential. 81,176 Considerably less invasive methods for studying human clocks in vivo comprise questionnaires, notably the Munich Chronotype Questionnaire, 177,178 along with simple measurements that can be conducted in the home environment of the participant, such as activity rhythm by actigraphy, 179 thoracic skin temperature measurement using contact thermometry, 180 or serial urine and saliva sampling followed by melatonin assessment. 137,181 These methods have yielded valuable information so far and should certainly be considered despite their reliability concern, mainly due to the imprecision of self-reporting and sample timing, or due to not wearing sensor devices regularly.…”