The DNA sequence patterns most predictive of liver activity across species matched a common set of transcription factors.

(a) Transcription factor analysis workflow. For each species enhancer classifier, we found TF motifs matched by the top 5% positively weighted 5-mers. Note that different 5-mers (marked with black box on the left) can match the same motif, e.g., MAFB and its reverse complement (RC). The overlap of matched TFs were then compared across each species’ classifier. (b) 33 of the TF motifs matched by the top 5% positive 5-mers from each GC-controlled liver classifier are shared in all species. The total number of TFs matched by top 5-mers in each species was: 121 (human), 104 (macaque), 100 (mouse), 81 (cow), 118 (dog), 102 (opossum). Similar results were observed for the non-GC-controlled classifier (S20 Fig). (c) The number of TFs matched by all species based on 5-mers in top positive, top negative, and 100 random sets of 5% of all possible 5-mers. The 33 TF motifs shared among the high-weight set for each species is thus significantly more than expected.