ArticlePLoS biology2014
Machine learning helps identify CHRONO as a circadian clock component.
Article in PLoS biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.
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Who cites it
76 citing papers in PubMed, 1 synthesis or guideline pooled it, 146 citations in OpenAlex.
- Mining for novel candidate clock genes in the circadian regulatory network.BMC systems biology · 2015Pooled it
- Interpretable machine learning reveals hemispheric asymmetry of state switching in the suprachiasmatic nucleus.Patterns (New York, N.Y.) · 2026Article
- A Chrono-Metabolic Approach to Mental Health: Current Perspectives on Circadian Rhythms, Gut Microbiota, and Microbial Metabolites in Mood Disorders.Metabolites · 2026Review
- Organoids: From Bench to Bedside Applications.MedComm · 2026Review
- Small-Molecule Modulation of the Circadian Clock in Cancer and Aging.Molecules (Basel, Switzerland) · 2026Review
- Chemical biology approaches to study and target circadian clocks and their components.FEBS letters · 2026Review
- Integrated miRNA-mRNA Atlas Reveals Temperature-Graded Brain Neuroendocrine Adaptation to Cold Stress in Silvery Pomfret (Biology · 2025Article
- CHRONO regulates the circadian clock via the REV-ERBα - BMAL1 loop.Npj biological timing and sleep · 2025Article
- Epigenetic Mechanisms in the Transcriptional Regulation of Circadian Rhythm in Mammals.Biology · 2025Review
- Comparative transcriptomic rhythms in the mouse and human prefrontal cortex.bioRxiv : the preprint server for biology · 2024Article
- The Relationship between Circadian Rhythm and Cancer Disease.International journal of molecular sciences · 2024Review
- Swimming exercise reverses transcriptomic changes in aging mouse lens.BMC medical genomics · 2024Article
- Comparative transcriptomic rhythms in the mouse and human prefrontal cortex.Frontiers in neuroscience · 2024Article
- Chronodisruption and Loss of Melatonin Rhythm, Associated with Alterations in Daily Motor Activity and Mitochondrial Dynamics in Parkinsonian Zebrafish, Are Corrected by Melatonin Treatment.Antioxidants (Basel, Switzerland) · 2023Article
- A multi-organoid platform identifies CIART as a key factor for SARS-CoV-2 infection.Nature cell biology · 2023Article
- Article
- Potential Role of the Circadian Clock in the Regulation of Cancer Stem Cells and Cancer Therapy.International journal of molecular sciences · 2022Review
- Mood phenotypes in rodent models with circadian disturbances.Neurobiology of sleep and circadian rhythms · 2022Review
- Experimental guidance for discovering genetic networks through hypothesis reduction on time series.PLoS computational biology · 2022Article
- Skeletal-Muscle-Specific Overexpression of Chrono Leads to Disruption of Glucose Metabolism and Exercise Capacity.Life (Basel, Switzerland) · 2022Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
Abstract
Over the last decades, researchers have characterized a set of "clock genes" that drive daily rhythms in physiology and behavior. This arduous work has yielded results with far-reaching consequences in metabolic, psychiatric, and neoplastic disorders. Recent attempts to expand our understanding of circadian regulation have moved beyond the mutagenesis screens that identified the first clock components, employing higher throughput genomic and proteomic techniques. In order to further accelerate clock gene discovery, we utilized a computer-assisted approach to identify and prioritize candidate clock components. We used a simple form of probabilistic machine learning to integrate biologically relevant, genome-scale data and ranked genes on their similarity to known clock components. We then used a secondary experimental screen to characterize the top candidates. We found that several physically interact with known clock components in a mammalian two-hybrid screen and modulate in vitro cellular rhythms in an immortalized mouse fibroblast line (NIH 3T3). One candidate, Gene Model 129, interacts with BMAL1 and functionally represses the key driver of molecular rhythms, the BMAL1/CLOCK transcriptional complex. Given these results, we have renamed the gene CHRONO (computationally highlighted repressor of the network oscillator). Bi-molecular fluorescence complementation and co-immunoprecipitation demonstrate that CHRONO represses by abrogating the binding of BMAL1 to its transcriptional co-activator CBP. Most importantly, CHRONO knockout mice display a prolonged free-running circadian period similar to, or more drastic than, six other clock components. We conclude that CHRONO is a functional clock component providing a new layer of control on circadian molecular dynamics.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.