The process by which cells replicate and pass on their genetic information, termed the cell cycle, is fundamental to life and has been intensely studied in the biological sciences. The past decade has witnessed an explosion in data derived from cell-cycle specific and other high-throughput experiments. These data include mRNA expression profiling using microarrays (^1?9), overexpression (¹⁰,¹¹) and knock-down studies (¹²), prediction of degradation signals (¹³), and systematic determination of kinase substrates (^14?16). Of particular interest are the mRNA profiling experiments, which are performed on samples aliquoted from synchronously growing cells progressing through the cell cycle. These studies provide a wealth of transcriptome data during the division process, which can be analyzed to deduce the subset of genes that are subjected to transcriptional regulation during the cell cycle. Gathering, comparing and analyzing such a vast amount of data require a significant effort.

In order to address the problems mentioned above, we developed Cyclebase (¹⁷), a web resource of cell-cycle microarray data sets and derived analysis results. The database was filled with over 20 time-series microarray experiments. In order to remove experimental condition differences and variation in the speed with which cells progress through the cell cycle, experimental data from each study were first normalized to a common time scale. Data from multiple studies were then plotted on a single chart for each gene. This intuitive visual representation, which depicts hundreds of experimental measurements in a single image, allows researchers to easily compare expression profiles across studies and gage the reproducibility of the experimental data. Each graph was supplemented by results from state-of-the-art analyses, including measures for periodicity, magnitude of regulation and the point in the division process when the transcription level is highest.

The first version of Cyclebase made it possible to easily assess transcriptional regulation of individual genes in single organisms. However, within the cell-cycle community there is a need for comparing both conservation of transcriptional regulation across species as well as assessing additional cell-cycle relevant information. To address these needs, we have expanded the functionality of Cyclebase, and further updated the database to account for changes in genomic annotations.

In order to provide easier access to more information about each genes? role in the cell cycle, we have performed a major update of Cyclebase. The Gene Details page, which is the centerpiece of the web site, contains many of these updates (Figure 1). This section highlights the major additions and changes to Cyclebase and describes its core components.

With the new functional improvements and the updated backend, Cyclebase is well positioned to store and present other temporal cell-cycle-related data sets, e.g. protein and phospho-protein expression profiles. Although only sparsely available right now, experiments that generate these types of data are expected to become more and more common in the future. Such data will help deconvolute the complexity of cell-cycle regulation, allowing researchers to further understand how regulatory mechanisms evolve, how differentiation and the cell cycle are intimately linked and how errors in the process can lead to complicated diseases such as cancer.

Novo Nordisk Foundation Center for Protein Research; Villum Kann Rasmussen Foundation. Funding for open access charge: Villum Kann Rasmussen Foundation.

Conflict of interest statement. None declared.

The authors wish to thank Hans-Henrik St?rfeldt, Kristoffer Rapacki and Peter W. Sackett for technical help with the database and Francesca Diella for help with providing data on phosphorylation sites.