Robust detection of periodic time series measured from biological systems

Ahdesmäki, Miika J.; Lähdesmäki, Harri; Pearson, Ronald K.; Huttunen, Heikki; Yli‐Harja, Olli

doi:10.1186/1471-2105-6-117

Cited by 111 publications

(68 citation statements)

References 23 publications

(61 reference statements)

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“…The time points were then permuted 50,000 times, and for each of the permutations, the Fourier transform was calculated together with the ratio of the F 24 Fourier component to the other components [52]. Expression data were fitted to a cosine curve.…”

Section: Methodsmentioning

confidence: 99%

System-Driven and Oscillator-Dependent Circadian Transcription in Mice with a Conditionally Active Liver Clock

et al. 2007

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The mammalian circadian timing system consists of a master pacemaker in neurons of the suprachiasmatic nucleus (SCN) and clocks of a similar molecular makeup in most peripheral body cells. Peripheral oscillators are self-sustained and cell autonomous, but they have to be synchronized by the SCN to ensure phase coherence within the organism. In principle, the rhythmic expression of genes in peripheral organs could thus be driven not only by local oscillators, but also by circadian systemic signals. To discriminate between these mechanisms, we engineered a mouse strain with a conditionally active liver clock, in which REV-ERBα represses the transcription of the essential core clock gene Bmal1 in a doxycycline-dependent manner. We examined circadian liver gene expression genome-wide in mice in which hepatocyte oscillators were either running or arrested, and found that the rhythmic transcription of most genes depended on functional hepatocyte clocks. However, we discovered 31 genes, including the core clock gene mPer2, whose expression oscillated robustly irrespective of whether the liver clock was running or not. By contrast, in liver explants cultured in vitro, circadian cycles of mPer2::luciferase bioluminescence could only be observed when hepatocyte oscillators were operational. Hence, the circadian cycles observed in the liver of intact animals without functional hepatocyte oscillators were likely generated by systemic signals. The finding that rhythmic mPer2 expression can be driven by both systemic cues and local oscillators suggests a plausible mechanism for the phase entrainment of subsidiary clocks in peripheral organs.

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Section: Methodsmentioning

confidence: 99%

System-Driven and Oscillator-Dependent Circadian Transcription in Mice with a Conditionally Active Liver Clock

et al. 2007

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“…5E), which Tu et al confirmed to be in the top 4% of periodic genes in yeast. HSP12, along with 43% of the genes identified by MINE but not Spellman et al , was also in the top third of statistically significant periodic genes in yeast according to the more sophisticated specialty statistic of Ahdesmaki et al ., which was specifically designed for finding periodic relationships without a pre-specified frequency in biological systems (24). Due to MIC's generality and the small size of this dataset ( n =24), relatively few of the genes analyzed (5%) had significant MIC scores after multiple testing correction at a false discovery rate of 5%.…”

Section: Application Of Mine To Real Datasetsmentioning

confidence: 99%

“…None of the examples except for (F) and (G) were detected by Spellman's analysis. However, subsequent studies have shown that (C-E) are periodic genes with longer wavelengths (22, 24). More plots of genes detected using MIC and MAS are given in Fig.…”

Section: Figurementioning

confidence: 99%

Detecting Novel Associations in Large Data Sets

Reshef

Finucane

et al. 2011

Science

2,520

1,942

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Identifying interesting relationships between pairs of variables in large datasets is increasingly important. Here, we present a measure of dependence for two-variable relationships: the maximal information coefficient (MIC). MIC captures a wide range of associations both functional and not, and for functional relationships provides a score that roughly equals the coefficient of determination (R2) of the data relative to the regression function. MIC belongs to a larger class of maximal information-based nonparametric exploration (MINE) statistics for identifying and classifying relationships. We apply MIC and MINE to datasets in global health, gene expression, major-league baseball, and the human gut microbiota, and identify known and novel relationships.

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“…Combined with a high level of stochastic noise, this makes the application of standard periodicity tests difficult due to insufficient statistical power. A number of algorithmic approaches have been applied recently to identify periodically expressed genes among thousands of time series profiles [8,9]. However, each of these methods only considers one gene expression profile at a time and lacks the statistical power to identify the circadian component in more than a small percentage of genes.…”

Section: Introductionmentioning

confidence: 99%

Digital Signal Processing Reveals Circadian Baseline Oscillation in Majority of Mammalian Genes

2007

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In mammals, circadian periodicity has been described for gene expression in the hypothalamus and multiple peripheral tissues. It is accepted that 10%–15% of all genes oscillate in a daily rhythm, regulated by an intrinsic molecular clock. Statistical analyses of periodicity are limited by the small size of datasets and high levels of stochastic noise. Here, we propose a new approach applying digital signal processing algorithms separately to each group of genes oscillating in the same phase. Combined with the statistical tests for periodicity, this method identifies circadian baseline oscillation in almost 100% of all expressed genes. Consequently, circadian oscillation in gene expression should be evaluated in any study related to biological pathways. Changes in gene expression caused by mutations or regulation of environmental factors (such as photic stimuli or feeding) should be considered in the context of changes in the amplitude and phase of genetic oscillations.

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Robust detection of periodic time series measured from biological systems

Cited by 111 publications

References 23 publications

System-Driven and Oscillator-Dependent Circadian Transcription in Mice with a Conditionally Active Liver Clock

System-Driven and Oscillator-Dependent Circadian Transcription in Mice with a Conditionally Active Liver Clock

Detecting Novel Associations in Large Data Sets

Digital Signal Processing Reveals Circadian Baseline Oscillation in Majority of Mammalian Genes

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