ArticleProceedings of the National Academy of Sciences of the United States of America2018
Universal method for robust detection of circadian state from gene expression.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
110 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Challenges and Recommendations for Integrating Circadian Medicine in Critical Care: A Roadmap.Chest · 2026Guideline
- Association between dim light melatonin onset predicted from gene expression profiles with sleep time and chronotype preference: A pilot study.Chronobiology international · 2025Trial
- Identification of a Preliminary Plasma Metabolome-based Biomarker for Circadian Phase in Humans.Journal of biological rhythms · 2021Trial
- BMAL1 in cardiovascular diseases: Molecular mechanisms, circadian regulation and translational perspectives (Review).Molecular medicine reports · 2026Review
- Chronotherapy in Oncology: Aligning Cancer Treatment with Biological Time.Journal of personalized medicine · 2026Review
- Unlocking the potential of circadian biology for cardiovascular health.Physiological reviews · 2026Review
- A gradual and sustainable approach to diagnosing sleep and circadian disturbances in dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Review
- Circadian rhythm-guided cellular therapy in hematologic malignancies: mechanisms, clinical evidence, and optimization strategies.Biomarker research · 2026Review
- Multi-Omics Landscape of Circadian Clock Dysregulation Across the Chronic Liver Disease Spectrum.International journal of molecular sciences · 2026Review
- Translational applications of circadian research: connecting chronobiology to medicine.Npj biological timing and sleep · 2026Review
- Transcriptional noise sets fundamental limits to decoding circadian clock phase from single-cell RNA snapshots.iScience · 2026Article
- HairTime: A noninvasive assay for estimating circadian phase from a single hair sample.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Research priorities to improve classification of sleep-wake disorders.Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 2026Review
- BAYESIAN RHYTHMIC MODEL FOR JOINTLY DETECTING CIRCADIAN BIOMARKERS AND PREDICTING MOLECULAR CIRCADIAN TIME IN HUMAN POST-MORTEM BRAIN TRANSCRIPTOME.bioRxiv : the preprint server for biology · 2026Article
- VIST: variational inference for single cell time series.Genome biology · 2026Article
- DCPR: a deep learning framework for circadian phase reconstruction.BMC bioinformatics · 2025Article
- Performance of Blood-Based Biomarkers for Human Circadian Pacemaker Phase: Training Sets Matter As Much As Feature-Selection Methods.Journal of biological rhythms · 2025Article
- Defining and detecting global transcriptional amplitude in circadian gene expression.bioRxiv : the preprint server for biology · 2025Article
- Circadian Regulation of Neuronal Membrane Capacitance-Mechanisms and Implications for Neural Computation and Behavior.International journal of molecular sciences · 2025Review
50 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
Authors and funding
8 authors.
Funding
Abstract
Circadian clocks play a key role in regulating a vast array of biological processes, with significant implications for human health. Accurate assessment of physiological time using transcriptional biomarkers found in human blood can significantly improve diagnosis of circadian disorders and optimize the delivery time of therapeutic treatments. To be useful, such a test must be accurate, minimally burdensome to the patient, and readily generalizable to new data. A major obstacle in development of gene expression biomarker tests is the diversity of measurement platforms and the inherent variability of the data, often resulting in predictors that perform well in the original datasets but cannot be universally applied to new samples collected in other settings. Here, we introduce TimeSignature, an algorithm that robustly infers circadian time from gene expression. We demonstrate its application in data from three independent studies using distinct microarrays and further validate it against a new set of samples profiled by RNA-sequencing. Our results show that TimeSignature is more accurate and efficient than competing methods, estimating circadian time to within 2 h for the majority of samples. Importantly, we demonstrate that once trained on data from a single study, the resulting predictor can be universally applied to yield highly accurate results in new data from other studies independent of differences in study population, patient protocol, or assay platform without renormalizing the data or retraining. This feature is unique among expression-based predictors and addresses a major challenge in the development of generalizable, clinically useful tests.
Indexed as
Identifiers
What OpenQuestion holds
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.