Advanced science (Weinheim, Baden-Wurttemberg, Germany)Jul 7, 2026

Connecting Body Clock Functions to Personalized Medicine Using Integrated Molecular Data

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jul 8, 2026

Abstract

Approximately 80% of FDA-approved drug targets show genotype-dependent rhythmicity.

Circadian rhythms play a role in various physiological processes, and their disruption is linked to increased disease risk.
An integrative multi-omics framework, RHINO, has been developed to explore circadian regulation and prioritize druggable targets.
Human genetic variation influences the expression of rhythmic genes across different contexts.
Circadian analyses across various cancers identify genes that consistently lose rhythmic expression, indicating potential vulnerabilities related to disease progression.
Upstream transcriptional regulators, including Estrogen Receptor α, are associated with disruptions in circadian rhythms.
Metabolic responses related to estrogen signaling show time-of-day-dependent variations in preclinical mouse models.

Simplified

Circadian rhythms are involved in nearly all physiological processes, and their disruption increases disease risk. Aligning drug administration timing with the body's internal clock, known as circadian medicine, holds promise for improving treatment efficacy and safety. However, systematic strategies to identify circadian-regulated therapeutic targets remain limited. Here, we develop RHINO (RHythmic Interacting Network for multi-Omics), an integrative multi-omics framework for exploring circadian regulation across diverse genetic and disease contexts, and prioritizing druggable circadian targets. Applying RHINO reveals that human genetic variation broadly shapes rhythmic gene expression, with approximately 80% of FDA-approved drug targets exhibiting genotype-dependent rhythmicity, thereby substantially expanding the druggable target landscape for more precise circadian medicine. Circadian analyses across cancer types and diseases further identify genes that consistently lose rhythmic expression, highlighting conserved circadian vulnerabilities linked to disease progression. Integrative regulatory analyses nominate upstream transcriptional regulators, including Estrogen Receptor α, associated with rhythmic disruption. Although the circadian rhythm of estrogen signaling has been recognized for decades, we show that this rhythmicity exhibits time-of-day-dependent metabolic responses in preclinical mouse models. Together, RHINO provides a community-accessible multi-omics platform that integrates genetic variation, disease-associated circadian remodeling, and regulatory inference to advance circadian medicine (https://hanlaboratory.com/RHINO).

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80% of FDA-approved drug targets show clock-dependent activity — timing may be everything

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Connecting Body Clock Functions to Personalized Medicine Using Integrated Molecular Data

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