Uncovering a Macrophage Transcriptional Program by Integrating Evidence from Motif Scanning and Expression Dynamics
Figure 6
Transcription factor genes associated with clusters in the inferred transcriptional network.
(A) The matrix shows associations between transcription factor genes and co-expressed gene clusters. Each column represents one of the 27 clusters within the inferred network, and each row represents one of the 36 transcription factor genes in the network. Clusters are ordered based on the LPS response time, defined as the time (under LPS stimulation) at which the cluster-median differential expression level reaches 25% of the maximum differential expression (see Materials and Methods, Expression Clustering). Transcription factor genes are ordered based on the LPS response time. The vertical gray line separates upregulated clusters (left half) from downregulated clusters (right half). The horizontal gray line separates upregulated transcription factors (top) from downregulated transcription factors (bottom). An orange or blue square indicates a statistically significant association between the transcription factor gene and the cluster, based on both promoter scanning and expression dynamics. An orange solid rectangle represents a positive average time-lagged correlation with genes in the cluster; a blue solid rectangle represents a negative average time-lagged correlation. (B) The red-green matrix is a heat-map showing transcription factor gene expression. The color indicates the normalized differential expression of the indicated transcription factor gene (over time), in LPS-stimulated wild-type macrophages (SDR, see Equation 1). Red indicates upregulation relative to unstimulated macrophages and green indicates downregulation. A diamond symbol indicates the transcription factor response time. (C) Each column of the red-green matrix indicates the median normalized differential expression of the genes in the indicated cluster (over time), in LPS-stimulated wild-type macrophages. The diamond indicates the average LPS response time of the genes within the cluster.