How to tell time: advances in decoding circadian phase from omics snapshots

The ability of organisms to keep track of external time, by means of the circadian clock interacting with the environment, is essential for health. The focus of this review is recent methods to detect the internal circadian time of an omics sample. Before reaching our main topic, we introduce the circadian clock, its hierarchical structure, and its main functions; we will also explain the notion of internal time, or circadian phase, and how it differs from the geophysical time. We then focus on the role played by the clock in the maintenance of human heath, in particular in the context of cancer. Thereafter, we analyze an important methodological question: how to infer the circadian phase of unlabeled omics snapshot measurements. Answering this question could both significantly increase our understanding of the circadian clock and allow the use of this knowledge in biomedical applications. We review existing methods, focusing on the more recent ones, following a historical trajectory. We explain the basic concepts underlying the methods, as well as some crucial technical aspects of each. We conclude by reporting how some of these methods have, more or less effectively, enabled furthering our understanding of the clock and given insights regarding potential biomedical applications.