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BMC Bioinformatics. 2009 Mar 26;10:96. doi: 10.1186/1471-2105-10-96.

Identifying significant temporal variation in time course microarray data without replicates.

Author information

1
Department of Mathematical and Statistical Sciences, University of Colorado, Denver, CO, USA. Stephen.Billups@ucdenver.edu

Abstract

BACKGROUND:

An important component of time course microarray studies is the identification of genes that demonstrate significant time-dependent variation in their expression levels. Until recently, available methods for performing such significance tests required replicates of individual time points. This paper describes a replicate-free method that was developed as part of a study of the estrous cycle in the rat mammary gland in which no replicate data was collected.

RESULTS:

A temporal test statistic is proposed that is based on the degree to which data are smoothed when fit by a spline function. An algorithm is presented that uses this test statistic together with a false discovery rate method to identify genes whose expression profiles exhibit significant temporal variation. The algorithm is tested on simulated data, and is compared with another recently published replicate-free method. The simulated data consists both of genes with known temporal dependencies, and genes from a null distribution. The proposed algorithm identifies a larger percentage of the time-dependent genes for a given false discovery rate. Use of the algorithm in a study of the estrous cycle in the rat mammary gland resulted in the identification of genes exhibiting distinct circadian variation. These results were confirmed in follow-up laboratory experiments.

CONCLUSION:

The proposed algorithm provides a new approach for identifying expression profiles with significant temporal variation without relying on replicates. When compared with a recently published algorithm on simulated data, the proposed algorithm appears to identify a larger percentage of time-dependent genes for a given false discovery rate. The development of the algorithm was instrumental in revealing the presence of circadian variation in the virgin rat mammary gland during the estrous cycle.

PMID:
19323838
PMCID:
PMC2682797
DOI:
10.1186/1471-2105-10-96
[Indexed for MEDLINE]
Free PMC Article

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