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Bayesian detection of non-sinusoidal periodic patterns in circadian expression data.

ABSTRACT: Cyclical biological processes such as cell division and circadian regulation produce coordinated periodic expression of thousands of genes. Identification of such genes and their expression patterns is a crucial step in discovering underlying regulatory mechanisms. Existing computational methods are biased toward discovering genes that follow sine-wave patterns.We present an analysis of variance (ANOVA) periodicity detector and its Bayesian extension that can be used to discover periodic transcripts of arbitrary shapes from replicated gene expression profiles. The models are applicable when the profiles are collected at comparable time points for at least two cycles. We provide an empirical Bayes procedure for estimating parameters of the prior distributions and derive closed-form expressions for the posterior probability of periodicity, enabling efficient computation. The model is applied to two datasets profiling circadian regulation in murine liver and skeletal muscle, revealing a substantial number of previously undetected non-sinusoidal periodic transcripts in each. We also apply quantitative real-time PCR to several highly ranked non-sinusoidal transcripts in liver tissue found by the model, providing independent evidence of circadian regulation of these genes.Matlab software for estimating prior distributions and performing inference is available for download from http://www.datalab.uci.edu/resources/periodicity/.Supplementary data are available at Bioinformatics online.

SUBMITTER: Chudova D

PROVIDER: S-EPMC3167694 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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Bayesian detection of non-sinusoidal periodic patterns in circadian expression data.

Chudova Darya D Ihler Alexander A Lin Kevin K KK Lin Kevin K KK Andersen Bogi B Smyth Padhraic P

Bioinformatics (Oxford, England) 20090922 23

<h4>Motivation</h4>Cyclical biological processes such as cell division and circadian regulation produce coordinated periodic expression of thousands of genes. Identification of such genes and their expression patterns is a crucial step in discovering underlying regulatory mechanisms. Existing computational methods are biased toward discovering genes that follow sine-wave patterns.<h4>Results</h4>We present an analysis of variance (ANOVA) periodicity detector and its Bayesian extension that can b ...[more]

PMID: 19773336

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Project description:BackgroundDetection of periodically expressed genes from microarray data without use of known periodic and non-periodic training examples is an important problem, e.g. for identifying genes regulated by the cell-cycle in poorly characterised organisms. Commonly the investigator is only interested in genes expressed at a particular frequency that characterizes the process under study but this frequency is seldom exactly known. Previously proposed detector designs require access to labelled training examples and do not allow systematic incorporation of diffuse prior knowledge available about the period time.ResultsA learning-free Bayesian detector that does not rely on labelled training examples and allows incorporation of prior knowledge about the period time is introduced. It is shown to outperform two recently proposed alternative learning-free detectors on simulated data generated with models that are different from the one used for detector design. Results from applying the detector to mRNA expression time profiles from S. cerevisiae showsthat the genes detected as periodically expressed only contain a small fraction of the cell-cycle genes inferred from mutant phenotype. For example, when the probability of false alarm was equal to 7%, only 12% of the cell-cycle genes were detected. The genes detected as periodically expressed were found to have a statistically significant overrepresentation of known cell-cycle regulated sequence motifs. One known sequence motif and 18 putative motifs, previously not associated with periodic expression, were also over represented.ConclusionIn comparison with recently proposed alternative learning-free detectors for periodic gene expression, Bayesian inference allows systematic incorporation of diffuse a priori knowledge about, e.g. the period time. This results in relative performance improvements due to increased robustness against errors in the underlying assumptions. Results from applying the detector to mRNA expression time profiles from S. cerevisiae include several new findings that deserve further experimental studies.

Dataset Information

Bayesian detection of non-sinusoidal periodic patterns in circadian expression data.

Publications

Bayesian detection of non-sinusoidal periodic patterns in circadian expression data.

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