Phase Coupled Meta-analysis: sensitive detection of oscillations in cell cycle gene expression, as applied to fission yeast

Here, we improve the detection of cell cycle oscillating genes by systematically taking into account the phase of peak gene expression. We design a novel meta-analysis measure based on vector addition: when a gene peaks or troughs in all experiments in the same phase of the cell cycle, the representative vectors add to produce a large final vector. Conversely, when the peaks in different experiments are in various phases of the cycle, vector addition produces a small final vector. We apply the measure to ten genome-wide cell cycle time course experiments from the fission yeast Schizosaccharomyces pombe, and detect many new, weakly oscillating genes.A very large fraction of all genes in S. pombe, perhaps one-quarter to one-half, show some cell cycle oscillation, although in many cases these oscillations may be incidental rather than adaptive.Cells reproduce and divide using an ordered set of processes. The cell division cycle is usually divided into four phases, called G1 (Gap 1), S (DNA Synthesis), G2 (Gap 2) and M (Mitosis). In late G1 phase, cells commit to a round of cell division, and in other ways prepare for the upcoming duplication; in S phase they replicate their DNA; in G2 they prepare for mitosis, and during mitosis they segregate their chromosomes, form two nuclei around these two sets of chromosomes, and finally the two new cells separate from one another. These ordered processes are extremely complex, involving hundreds if not thousands of proteins. These processes are regulated and assisted by changes in gene transcription: that is, many genes needed for DNA synthesis are transcribed just before S phase; many genes needed for mitosis are transcribed just before M phase, and so on. Genes regulated in this way - i.e., expressed at a particular time in the cell division cycle, with the effect of aiding progress through a particular part of the cell division cycle - are called cell cycle regulated genes.In principle, there might be two kinds of genes whose