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Figure 2 | Clinical and Translational Medicine

Figure 2

From: Psoriasis drug development and GWAS interpretation through in silico analysis of transcription factor binding sites

Figure 2

PRE motifs significantly enriched in sequences upstream of psoriasis-increased DEGs. We identified 126 PWM models matching motifs significantly enriched in sequences upstream of PP-increased DEGs (FDR < 0.10). (A) The 126 motifs were clustered based upon k-mer scores (HOPACH algorithm), leading to the identification of two motif sub-groups (blue and green, respectively). The shown k-mers were chosen by dividing the dendrogram into branches and identifying the 3- or 4-mer for which k-mer scores (yellow-black heatmap; see Methods) were most significantly elevated among motifs within a given branch. Red-black heatmaps show enrichment scores indicating how similar a PWM is to other PWMs associated with DNA-binding domain superfamily and class groups. To calculate such scores for a given motif, we first screened the 2935 PWMs to identify the 10% most similar “nearest neighbor” PWMs (Pearson correlation). We then assessed whether PWMs from a given superfamily or class were enriched among nearest neighbors (Fisher’s Exact Test), and the p-value from this test was used to calculate the enrichment score (−log10(p-value)). (B) Number of motifs associated with DNA-binding domain superfamilies. P-values assess whether motifs belonging to a superfamily are overrepresented among the 126 PRE motifs (right margin; Fisher’s Exact Test; asterisks denote FDR < 0.05). (C) Number of motifs associated with DNA-binding domain classes (top 10). P-values assess whether motifs from a given class are overrepresented among the 126 PRE motifs (right margin; Fisher’s Exact Test; asterisks denote FDR < 0.05).

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