# Real-time breath metabolomics: A new direction for circadian biomarkers

> **NIH NIH R21** · BRIGHAM AND WOMEN'S HOSPITAL · 2022 · $179,000

## Abstract

ABSTRACT
The goal of the project is to optimize human health, performance, and safety by developing robust
diagnostic biomarkers for circadian timing to identify, from a single biospecimen, the biological time within
an individual. Our understanding of the importance of circadian timing to human health is increasing;
disruption of circadian timing is associated with metabolic disorders, cardiovascular disease, immune
dysregulation, and cancers. A recent study tested ~17,000 genes and found that nearly half cycled in at
least one human tissue, and more than 900 of those cycling genes coded for proteins that are drug
targets, transport drugs, or are involved in drug metabolism. Building on this emerging knowledge, we
should be able to regularize circadian timing to prevent disease, and to administer many short half-life
drugs at their ideal circadian time to increase efficacy and/or reduce side effects. However, our ability to
incorporate circadian timing into clinical decision-making and treatment is impaired by our current inability
to measure circadian phase quickly and easily.
Current methods for assessing circadian timing require sampling over hours (or even up to a day) while
the patient is in controlled conditions. In the parent grant we aim to develop methods that can estimate
individual circadian time with a single blood sample taken at any time of the day or night using a plasma
proteomics-based method to identify a panel of rhythmic proteins, as well as refining a monocyte-based
method using a panel of 15 transcripts. In this New Research Direction project, we will expand our
circadian biomarker efforts to include development of a breath biomarker for circadian timing.
We will use real-time breath metabolomics technology called selected-ion flow-tube mass
spectrometry (SIFT-MS) to search for breath biomarkers of circadian time. We will add collection of
breath samples every 3 hours to the studies in the parent grant, using the rigorous constant routine
methodology in highly controlled laboratory conditions to ensure any observed oscillations in breath
metabolites are due to endogenous variations in breath components rather than representing responses
to changes in activity, food/fluid intake or composition, or sleep-wake state. We will validate the breath
metabolomics biomarker against circadian phase estimate derived from plasma melatonin (the current
“gold-standard” phase marker). When fully developed, this breath-based method will enable on-demand
monitoring of circadian status non-invasively and in real-time. The proposed New Research Direction
project has the potential to develop a rapid, real-time, non-invasive method for diagnosis and treatment
of patients with suspected circadian rhythm disorders (delayed sleep-wake phase disorder, shift work
disorder) and other sleep pathologies (insomnia, hypersomnia) and to advance the potential of
personalized medicine through individualized treatment timing (chronomedicine).
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## Key facts

- **NIH application ID:** 10526014
- **Project number:** 1R21HL161464-01A1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Charles A Czeisler
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $179,000
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10526014

## Citation

> US National Institutes of Health, RePORTER application 10526014, Real-time breath metabolomics: A new direction for circadian biomarkers (1R21HL161464-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10526014. Licensed CC0.

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