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Uncovering a Macrophage Transcriptional Program by Integrating Evidence from Motif Scanning and Expression Dynamics

Figure 5

Patterns of high-confidence motif enrichments within promoters of target clusters reveal associations between regulatory elements and expression patterns.

Each row in the matrix represents a TF binding element, and each column represents a cluster of differentially expressed genes. Clusters are ordered as in Figure 2, and thus are grouped hierarchically by similarity of their extremal expression fold-change under the four TLR agonists LPS, Pam3CSK4, poly I:C, and R848. Each motif (row) is associated with one or more position-weight matrices (the V$ prefix and numeric suffixes are omitted, and results for multiple position-weight matrices representing the same motif were combined for each column, by taking the matrix with the maximum number of matches within the indicated cluster). Each colored block in the matrix indicates pair of a motif and target cluster for which the fraction of genes in the cluster with a motif match, is enriched relative to the overall fraction of genes expressed in the macrophage that possess the motif (P≤10−2, Fisher's exact test). The color of each matrix element (block) in the interior of the figure indicates the fraction scanned of genes within the cluster containing at least one match for the indicated motif. The number of scanned genes within the cluster that contained a match for the indicated motif is shown in yellow typeface. The red/green colored blocks above the top horizontal axis shows whether each cluster is upregulated (red) or downregulated (green) at its most extremal fold-change under stimulation with the aforementioned TLR agonists. The hatched green/red pattern indicates a cluster whose extremal fold-change direction (up/down) is stimulus-dependent (see Figure 2). The colored (blue, cyan, orange, yellow, purple) blocks above the top of the matrix indicate the likely pathway through which the cluster is differentially expressed; the color scheme corresponds to that shown in the dendrogram in Figure 2.

Figure 5

doi: https://doi.org/10.1371/journal.pcbi.1000021.g005