Figure 5

Design of a complex decoy oligonucleotide (cdODN) directed against TFs activated in psoriasis lesions (FOXM1, ISGF3, IRF1 and NF-κB). (A) Psoriasis cdODN199. The proposed design consists of consensus sequences from four PRE motifs significantly enriched in sequences upstream of PP-increased DEGs (FDR < 0.10). cdODN199 was chosen from among 384 possible combinations of the four PRE sequences (see text). 5-TTTC/GAAA-3 elements are shown with red font. (B) Top-ranked dODN molecules most closely matching PWM motifs enriched in sequences upstream of PP-increased DEGs. Each dODN was evaluated to identify matching motifs within our dictionary (2935 PWMs; ψ/ψ _max > 0.80, see Methods). The number of PWM matches is indicated (left) along with Z statistics (right), reflecting enrichment of matching motifs in sequences upstream of PP-increased DEGs. The PWM most closely matching each dODN is listed (right margin). Further details for each dODN can be obtained from the PubMed ID (left margin in parentheses). Parts (C) – (F) show the top 10 PWM models most closely matching (C) cdODN199, (D) STAT3 (15592573), (E) AP1 (23223130) and (F) STAT6 (23146666). dODN sequences are listed (bottom margin) and each figure shows consensus sequences for best-matching PWMs. Match scores are listed in the right margin (see Methods, Equation 2). The [0, 1] probability preference (PPM value) for each base is indicated by the color scale (right).