Microarray analysis reveals clock-related gene expression signature.

<p>(<b>A</b>) Shown is the heatmap generated with the list of 45 discriminative genes. Heatmaps were generated using Pearson distance function and ward clustering. Colour bar (left) indicates the expression levels for genes in the array, from green (low expression) to red (high expression). Colour bar (top) indicates class membership. Blue indicates strong oscillator, red indicates weak oscillator, and green indicates test sample (U2OS). Genes are ordered by profile similarity. (<b>B</b>) A comprehensive regulatory network of the mammalian circadian clock. We used a curated text mining approach to search for interactions between our genes of interest. The network represents 108 novel interactions, supported by 132 PubMed references. In the core of the network (orange circles) the main components of the canonical feedback loops are shown. The outer shell of the network (grey circles) shows the clock-regulated genes and proteins feeding back to the core components and thereby potentially influencing the oscillations. Red lines represent inhibitory interactions; green lines, activating interactions; grey lines, other kinds of interactions. A large format of the network is provided as <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004338#pgen.1004338.s002" target="_blank">Figure S2</a>. (<b>C, D</b>) Networks of circadian and cancer regulation for the discriminative genes. All networks were generated using the GeneView software (expected rate of false positive interactions, 10%) with additional data retrieved from the STRING database. (<b>C</b>) Network of interaction correlating circadian clock genes (all genes in (B)) and discriminative genes. A large format of the network is provided as <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004338#pgen.1004338.s003" target="_blank">Figure S3</a>. (<b>D</b>) Network of interaction correlating discriminative genes and cancer genes. A large format of the network is provided as <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004338#pgen.1004338.s004" target="_blank">Figure S4</a>. Cancer-related genes are represented in orange, clock genes in blue, discriminative genes in green and common genes in violet (e.g. TNFα). Grey lines represent text-mined interactions, blue lines interactions from the STRING database, and yellow lines common interactions. A list of colon specific interactions (by filtering for colon cancer related terms) is given in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004338#pgen.1004338.s009" target="_blank">Table S2</a>.