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- Title
Improved Statistical Methods Enable Greater Sensitivity in Rhythm Detection for Genome-Wide Data.
- Authors
Hutchison, Alan L.; Maienschein-Cline, Mark; Chiang, Andrew H.; Tabei, S. M. Ali; Gudjonson, Herman; Bahroos, Neil; Allada, Ravi; Dinner, Aaron R.
- Abstract
Robust methods for identifying patterns of expression in genome-wide data are important for generating hypotheses regarding gene function. To this end, several analytic methods have been developed for detecting periodic patterns. We improve one such method, JTK_CYCLE, by explicitly calculating the null distribution such that it accounts for multiple hypothesis testing and by including non-sinusoidal reference waveforms. We term this method empirical JTK_CYCLE with asymmetry search, and we compare its performance to JTK_CYCLE with Bonferroni and Benjamini-Hochberg multiple hypothesis testing correction, as well as to five other methods: cyclohedron test, address reduction, stable persistence, ANOVA, and F24. We find that ANOVA, F24, and JTK_CYCLE consistently outperform the other three methods when data are limited and noisy; empirical JTK_CYCLE with asymmetry search gives the greatest sensitivity while controlling for the false discovery rate. Our analysis also provides insight into experimental design and we find that, for a fixed number of samples, better sensitivity and specificity are achieved with higher numbers of replicates than with higher sampling density. Application of the methods to detecting circadian rhythms in a metadataset of microarrays that quantify time-dependent gene expression in whole heads of Drosophila melanogaster reveals annotations that are enriched among genes with highly asymmetric waveforms. These include a wide range of oxidation reduction and metabolic genes, as well as genes with transcripts that have multiple splice forms.
- Subjects
GENOMES; RHYTHMIC modes; GENE fusion; OXIDATION-reduction reaction; GENE expression
- Publication
PLoS Computational Biology, 2015, Vol 11, Issue 3, p1
- ISSN
1553-734X
- Publication type
Article
- DOI
10.1371/journal.pcbi.1004094