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Genome-wide circadian rhythm detection methods: systematic evaluations and practical guidelines.

ABSTRACT: Circadian rhythms are oscillations of behavior, physiology and metabolism in many organisms. Recent advancements in omics technology make it possible for genome-wide profiling of circadian rhythms. Here, we conducted a comprehensive analysis of seven existing algorithms commonly used for circadian rhythm detection. Using gold-standard circadian and non-circadian genes, we systematically evaluated the accuracy and reproducibility of the algorithms on empirical datasets generated from various omics platforms under different experimental designs. We also carried out extensive simulation studies to test each algorithm's robustness to key variables, including sampling patterns, replicates, waveforms, signal-to-noise ratios, uneven samplings and missing values. Furthermore, we examined the distributions of the nominal $P$-values under the null and raised issues with multiple testing corrections using traditional approaches. With our assessment, we provide method selection guidelines for circadian rhythm detection, which are applicable to different types of high-throughput omics data.

SUBMITTER: Mei W

PROVIDER: S-EPMC8138819 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Genome-wide circadian rhythm detection methods: systematic evaluations and practical guidelines.

Mei Wenwen W Jiang Zhiwen Z Chen Yang Y Chen Li L Sancar Aziz A Jiang Yuchao Y

Briefings in bioinformatics 20210501 3

Circadian rhythms are oscillations of behavior, physiology and metabolism in many organisms. Recent advancements in omics technology make it possible for genome-wide profiling of circadian rhythms. Here, we conducted a comprehensive analysis of seven existing algorithms commonly used for circadian rhythm detection. Using gold-standard circadian and non-circadian genes, we systematically evaluated the accuracy and reproducibility of the algorithms on empirical datasets generated from various omic ...[more]

PMID: 32672832

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Project description:BackgroundCircadian variation of gene expression is often neglected when ionizing radiation-induced effects are studied, whether in animal models or in cell culture. This study characterized diurnal variation of genome-wide transcriptional regulation and responses of potential biomarkers and signature genes in normal mouse tissues at 24 h after i.v. administration of (131)I.MethodsFemale BALB/c nude mice were i.v. injected with 90 kBq (131)I at 9:00 a.m., 12:00 p.m., or 3:00 p.m. and killed after 24 h (n = 4/group). Paired control groups were mock-treated (n = 3-4/group). The kidneys, liver, lungs, spleen, and thyroid were excised, snap-frozen, and stored at -80 °C until extraction of total RNA. RNA microarray technology was used for genome-wide expression analysis. Enriched biological processes were categorized after cellular function. Signature genes for ionizing radiation and thyroid hormone-induced responses were taken from the literature. Absorbed dose was estimated using the Medical Internal Radiation Dose (MIRD) formalism.ResultsThe thyroid received an absorbed dose of 5.9 Gy and non-thyroid tissues received 0.75-2.2 mGy over 24 h. A distinct peak in the total number of significantly regulated transcripts was observed at 9:00 a.m. in the thyroid, but 3 h later in the kidney cortex, kidney medulla, and liver. Transcriptional regulation in the lungs and spleen was marginal. Associated cellular functions generally varied in quality and response strength between morning, noon, and afternoon. In the thyroid, 25 genes were significantly regulated at all investigated times of day, and 24 thereof showed a distinct pattern of pronounced down-regulation at 9:00 a.m. and comparatively weak up-regulation at later times. Eleven of these genes belonged to the species-specific kallikrein subfamily Klk1b. Responses in signature genes for thyroid hormone-induced responses were more frequent than for ionizing radiation, and trends persisted irrespective of time of day.ConclusionDiurnal variation of genome-wide transcriptional responses to 90 kBq (131)I was demonstrated for the thyroid, kidney cortex and medulla, and liver, whereas variation was only marginal in the lungs and spleen. Overall, significant detection of potential biomarkers and signature genes was validated at each time of day, although direction of regulation and fold-change differed between morning, noon, and afternoon. These findings suggest that circadian rhythm should be considered in radiation research and that biological and analytical endpoints should be validated for circadian robustness.

Project description:BackgroundIndividuals with typical circadian rhythm sleep-wake disorders (CRSWDs) have a habitual sleep timing that is desynchronized from social time schedules. However, it is possible to willfully force synchronisation against circadian-driven sleepiness, which causes other sleep problems. This pathology is distinguishable from typical CRSWDs and is referred to here as latent CRSWD (LCRSWD). Conventional diagnostic methods for typical CRSWDs are insufficient for detecting LCRSWD because sufferers have an apparently normal habitual sleep timing.MethodsWe first evaluated the reliability of circadian phase estimation based on clock gene expression using hair follicles collected at three time points without sleep interruption. Next, to identify detection criteria for LCRSWD, we compared circadian and sleep parameters according to estimated circadian phases, at the group and individual level, between subjects with low and high Pittsburgh Sleep Quality Index (PSQI) scores. To validate the reliability of identified detection criteria, we investigated whether the same subjects could be reproducibly identified at a later date and whether circadian amelioration resulted in sleep improvement.FindingsWe successfully validated the reliability of circadian phase estimation at three time points and identified potential detection criteria for individuals with LCRSWD attributed to delayed circadian-driven sleepiness. In particular, a criterion based on the interval between the times of the estimated circadian phase of clock gene expression and getting out of bed on work or school days was promising. We also successfully confirmed the reproducibility of candidate screening and sleep improvement by circadian amelioration, supporting the reliability of the detection criteria.InterpretationAlthough several limitations remain, our present study demonstrates a promising prototype of a detection method for LCRSWD attributed to delayed circadian-driven sleepiness. More extensive trials are needed to further validate this method.FundingThis study was supported mainly by JSPS, Japan.

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Genome-wide circadian rhythm detection methods: systematic evaluations and practical guidelines.

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Genome-wide circadian rhythm detection methods: systematic evaluations and practical guidelines.

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