The more the merrier: comparative analysis of microarray studies on cell cycle-regulated genes in fission yeast.
The last two years have seen the publication of three genome-wide gene expression studies of the fission yeast cell cycle. While these microarray papers largely agree on the main patterns of cell cycle-regulated transcription and its control, there are discrepancies with regard to the identity and numbers of periodically expressed genes. We present benchmark and reproducibility analyses showing that the main discrepancies do not reflect differences in the data themselves (microarray or synchronization methods seem to lead only to minor biases) but rather in the interpretation of the data. Our reanalysis of the three datasets reveals that combining all independent information leads to an improved identification of periodically expressed genes. These evaluations suggest that the available microarray data do not allow reliable identification of more than about 500 cell cycle-regulated genes. The temporal expression pattern of the top 500 periodically expressed genes is generally consistent across experiments and the three studies, together with our integrated analysis, provide a coherent and rich source of information on cell cycle-regulated gene expression in Schizosaccharomyces pombe. The reanalysed datasets and other supplementary information are available from an accompanying website: http://www.cbs.dtu.dk/cellcycle/. We hope that this paper will resolve the apparent discrepancies between the previous studies and be useful both for wet-lab biologists and for theoretical scientists who wish to take advantage of the data for follow-up work.
Cancer Research UK Fission Yeast Functional Genomics Group, Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
Samuel
S
Marguerat
Center for Biological Sequence Analysis, BioCentrum-DTU, Technical University of Denmark, DK-2800 Lyngby, Denmark.
Thomas S
TS
Jensen
Center for Biological Sequence Analysis, BioCentrum-DTU, Technical University of Denmark, DK-2800 Lyngby, Denmark.
Ulrik
U
de Lichtenberg
Cancer Research UK Fission Yeast Functional Genomics Group, Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
Brian T
BT
Wilhelm
EMBL Heidelberg, Meyerhofstrasse 1, D-69117 Heidelberg, Germany.
Lars J
LJ
Jensen
Cancer Research UK Fission Yeast Functional Genomics Group, Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
Jürg
J
Bähler
D002453:Cell Cycle / Q000235:genetics*; D019295:Computational Biology / Q000379:methods; D015966:Gene Expression Regulation, Fungal / Q000235:genetics*; D005810:Multigene Family / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D012568:Schizosaccharomyces / Q000166:cytology* / Q000235:genetics*