Time-course expression profiles and methods for spectrum analysis have been applied for detecting transcriptional periodicities, which are valuable patterns to unravel genes associated with cell cycle and circadian rhythm regulation. However, most of the proposed methods suffer from restrictions and large false positives to a certain extent. Additionally, in some experiments, arbitrarily irregular sampling times as well as the presence of high noise and small sample sizes make accurate detection a challenging task. A novel scheme for detecting periodicities in time-course expression data is proposed, in which a real-valued iterative adaptive approach (RIAA), originally proposed for signal processing, is applied for periodogram estimation. The inferred spectrum is then analyzed using Fisher’s hypothesis test. With a proper -value threshold, periodic genes can be detected. A periodic signal, two nonperiodic signals, and four sampling strategies were considered in the simulations, including both bursts and drops. In addition, two yeast real datasets were applied for validation. The simulations and real data analysis reveal that RIAA can perform competitively with the existing algorithms. The advantage of RIAA is manifested when the expression data are highly irregularly sampled, and when the number of cycles covered by the sampling time points is very reduced. 1. Introduction Patterns of periodic gene expression have been found to be associated with essential biological processes such as cell cycle and circadian rhythm [1], and the detection of periodic genes is crucial to advance our understanding of gene function, disease pathways, and, ultimately, therapeutic solutions. Using high-throughput technologies such as microarrays, gene expression profiles at discrete time points can be derived and hundreds of cell cycle regulated genes have been reported in a variety of species. For example, Spellman et al. applied cell synchronization methods and conducted time-course gene expression experiments on Saccharomyces cerevisiae [2]. The authors identified 800 cell cycle regulated genes using DNA microarrays. Also, Rustici et al. and Menges et al. identified 407 and about 500 cell cycle regulated genes in Schizosaccharomyces pombe and Arabidopsis, respectively [3, 4]. Signal processing in the frequency domain simplifies the analysis and an emerging number of studies have demonstrated the power of spectrum analysis in the detection of periodic genes. Considering the common issues of missing values and noise in microarray experiments, Ahdesm？ki et al. proposed a
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