Significant and unique HOSVD combinations, that is, subtensors (Table I and Supplementary Figures 8–11). (A) Bar charts for the fractions of mRNA expression that the seven most significant combinations capture in the data cuboid. The fourth combination S(4,1,2), of the fourth pattern across the genes, the first across the time points and the second across the biological conditions, captures ∼2.7% of the expression of the 4270 genes. (B) Line-joined graphs of the first (red), second (blue) and third (green) expression patterns across the time points. The color bars indicate the cell cycle classifications of the time points in the averaged Cdc6⁺/45⁺ control (Supplementary Figure 7) as described (Spellman et al, 1998): M/G1 (yellow), G1 (green), S (blue), S/G2 (red) and G2/M (orange). The grid line separates the even and odd hybridization batches, indicated by black arrows. The first pattern is approximately time invariant. The second and third patterns describe oscillations consistent within the hybridization batches, that peak at the M/G1 and G1/S phases and trough at the S/G2 and G2/M phases, respectively. (C) Line-joined graphs of the first (red), second (blue) and third (green) patterns across the conditions. The first pattern is condition invariant. The second pattern correlates with underexpression in both conditions in which DNA replication is prevented, that is, in both Cdc6⁻ and Cdc45⁻ cells, relative to the averaged Cdc6⁺/45⁺ control. The third pattern correlates with overexpression in the Cdc6⁻ cells and underexpression in the Cdc45⁻ cells relative to the averaged control.

DNA replication-dependent and Mcm2–7 origin binding-dependent gene expression. Raster display, in which the expression of each gene is centered at its time-invariant level. (A) DNA replication is required for efficient histone gene expression. Raster display of histone gene expression shows that histone genes are overexpressed in the Cdc6⁺/45⁺ control, relative to the Cdc6⁻ condition, and to a lesser extent also relative to the Cdc45⁻ condition, in a highly correlated manner. (B) Origin licensing decreases the expression of genes with origins near their 3′ ends. Raster display of the expression of the 16 most significant genes in this class shows that these genes are overexpressed in the Cdc6⁻ relative to the Cdc45⁻ time courses, and to a lesser extent also relative to the control, in a manner less correlated than that of the histone genes.

The averaged data cuboid of mRNA expression of the 4270 genes across the 12 time points and across the three biological conditions (Supplementary information Dataset 3). Raster display with overexpression (red), no change in expression (black) and underexpression (green), where the expression of each gene is centered at its time-invariant level. The genes are sorted by their angular distances θ_:=arctan(U_:3/U_:2) between the second and third HOSVD combinations (Supplementary information Section 2.6), which represent the unperturbed cell cycle expression oscillations (Box 1 and Supplementary Figure 12). The white lines separate the even and odd hybridization batches, indicated by black arrows. The picture of global expression oscillations in the averaged Cdc6⁺/45⁺ control time course is consistent with previous genome-wide mRNA expression analyses of synchronized Saccharomyces cerevisiae cultures (Alter et al, 2000; Alter and Golub, 2004; Alter, 2006; Li and Klevecz, 2006; Klevecz et al, 2008). The picture that emerges is that of unperturbed global expression oscillations that are dominant in the Cdc6⁻, Cdc45⁻ as well as in the Cdc6⁺/45⁺ time courses.