Bottleneck genes and community structure in the cell cycle network of S. pombe

The identification of cell cycle-related genes is still a difficult task, even for organisms with relatively few genes such as the fission yeast. Several gene expression studies have been published on S. pombe showing similarities but also discrepancies in their results. We introduce a network in which the weight of each link is a function of the phase difference between the expression peaks of two genes. The analysis of the stability of the clustering through the computation of an entropy parameter reveals a structure made of four clusters, the first one corresponding to a robustly connected M-G1 component, the second to genes in the S phase, and the third and fourth to two G2 components. They are separated by bottleneck structures that appear to correspond to cell cycle checkpoints. We identify a number of genes that are located on these bottlenecks. They represent a novel group of cell cycle regulatory genes. They all show interesting functions, and they are supposed to be involved in the regulation of the transition from one phase to the next. We therefore present a comparison of the available studies on the fission yeast cell cycle and a general statistical bioinformatics methodology to find bottlenecks and gene community structures based on recent developments in network theory. © 2007 Caretta-Cartozo et al.