Figure 5: Cross-species transcription factor motif analysis reveals major drivers of cuSCC development.

(a) Global view of transcription factors with target genes enriched across the entire NS/CHR to AK/PAP to cuSCC progression sequence. Directionality reflects the significant upregulation (above the line) or downregulation (below the line) of predicted targets of the listed transcription factors. Some factors have targets that are enriched in opposite directions across distinct transitions. The transcription factors highlighted in red were identified in both TRANSFAC and LME-based analyses. (b) Network analysis demonstrates that core transcriptional drivers are highly interconnected in both human (left) and mouse (right). The bolded lines delineate connections that are significant by Fisher exact test (P<10⁻⁴). (c) The LME model of mRNA expression changes across cuSCC development in both species demonstrates that the vast majority of significant gene expression changes occur in the early transition from NS/CHR to AK/PAP.