Figure 1.

Method overview. (a) Genes (nodes in the graph) are connected to other genes based on sequence similarity. Species identity is indicated by shape of nodes. Genes are also connected to a 'score node', which represents cycling expression score. Information is propagated along the edges until convergence. Genes are assigned a posterior score and a cut-off is applied to select the top genes for each species. (b) The subgraph containing the selected genes is further analyzed by identifying multidomain homology cliques. Examples of identified cliques of conserved genes are presented in panels c to f. (c) Cyclins. Fission yeast Cig2 promotes the onset of S phase [45]. Human Ccna2 is part of the G2 checkpoint [46]. (d) Cdc6/Cdc18 is a conserved and essential component of pre-replication complexes (pre-RCs). Orc1 is the largest subunit of the origin recognition complex (ORC), which binds specifically to replication origins and triggers the assembly of pre-RCs [47]. (e) TOG related proteins, a family of microtubule-associated proteins (MAPs). Proteins in this group localize to the plus-end tips of microtubules and are essential for spindle pole organization. Alp14 is a component of the Mad2-dependent spindle checkpoint cascade sharing redundant functions with Dis1. Mutants with both genes knocked out are nonviable [48]. (f,g) Microtubule component clique and expression profiles for fission yeast Nda3 in eight experiments [4-6]. Nda3, a known cell division gene [49], obtains a high cycling score but is not one of the 600 top cycling fission genes based on expression analysis. Using our method, its score is correctly elevated because its sequence similarity to high scoring genes.