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Bootstrapping and Empirical Bayes Methods Improve Rhythm Detection in Sparsely Sampled Data.

ABSTRACT: There is much interest in using genome-wide expression time series to identify circadian genes. However, the cost and effort of such measurements often limit data collection. Consequently, it is difficult to assess the experimental uncertainty in the measurements and, in turn, to detect periodic patterns with statistical confidence. We show that parametric bootstrapping and empirical Bayes methods for variance shrinkage can improve rhythm detection in genome-wide expression time series. We demonstrate these approaches by building on the empirical JTK_CYCLE method (eJTK) to formulate a method that we term BooteJTK. Our procedure rapidly and accurately detects cycling time series by combining information about measurement uncertainty with information about the rank order of the time series values. We exploit a publicly available genome-wide data set with high time resolution to show that BooteJTK provides more consistent rhythm detection than existing methods at typical sampling frequencies. Then, we apply BooteJTK to genome-wide expression time series from multiple tissues and show that it reveals biologically sensible tissue relationships that eJTK misses. BooteJTK is implemented in Python and is freely available on GitHub at https://github.com/alanlhutchison/BooteJTK .

SUBMITTER: Hutchison AL

PROVIDER: S-EPMC6347739 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Bootstrapping and Empirical Bayes Methods Improve Rhythm Detection in Sparsely Sampled Data.

Hutchison Alan L AL Allada Ravi R Dinner Aaron R AR

Journal of biological rhythms 20180801 4

There is much interest in using genome-wide expression time series to identify circadian genes. However, the cost and effort of such measurements often limit data collection. Consequently, it is difficult to assess the experimental uncertainty in the measurements and, in turn, to detect periodic patterns with statistical confidence. We show that parametric bootstrapping and empirical Bayes methods for variance shrinkage can improve rhythm detection in genome-wide expression time series. We demon ...[more]

PMID: 30101659

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Project description:BackgroundMicroarray data enables the high-throughput survey of mRNA expression profiles at the genomic level; however, he data presents a challenging statistical problem because of the large number of transcripts with small sample sizes that are obtained. To reduce the dimensionality, various Bayesian or empirical Bayes hierarchical models have been developed. However, because of the complexity of the microarray data, no model can explain the data fully. It is generally difficult to scrutinize the irregular patterns of expression that are not expected by the usual statistical gene by gene models.ResultsAs an extension of empirical Bayes (EB) procedures, we have developed the β-empirical Bayes (β-EB) approach based on a β-likelihood measure which can be regarded as an 'evidence-based' weighted (quasi-) likelihood inference. The weight of a transcript t is described as a power function of its likelihood, fβ(yt|θ). Genes with low likelihoods have unexpected expression patterns and low weights. By assigning low weights to outliers, the inference becomes robust. The value of β, which controls the balance between the robustness and efficiency, is selected by maximizing the predictive β₀-likelihood by cross-validation. The proposed β-EB approach identified six significant (p<10⁻⁵) contaminated transcripts as differentially expressed (DE) in normal/tumor tissues from the head and neck of cancer patients. These six genes were all confirmed to be related to cancer; they were not identified as DE genes by the classical EB approach. When applied to the eQTL analysis of Arabidopsis thaliana, the proposed β-EB approach identified some potential master regulators that were missed by the EB approach.ConclusionsThe simulation data and real gene expression data showed that the proposed β-EB method was robust against outliers. The distribution of the weights was used to scrutinize the irregular patterns of expression and diagnose the model statistically. When β-weights outside the range of the predicted distribution were observed, a detailed inspection of the data was carried out. The β-weights described here can be applied to other likelihood-based statistical models for diagnosis, and may serve as a useful tool for transcriptome and proteome studies.

Dataset Information

Bootstrapping and Empirical Bayes Methods Improve Rhythm Detection in Sparsely Sampled Data.

Publications

Bootstrapping and Empirical Bayes Methods Improve Rhythm Detection in Sparsely Sampled Data.

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