The read-across hypothesis can be viewed simply as what we see in one species is likely to be reflected in others, that conserve the same target, at the level of a pharmacological response (mode of action); that is, we see the same end result.
The adenosine nucleotide on the 3' end of the forward primer does not match the primer binding region in birds, but is conserved in the target prey groups (Table S1).
A regulation is only considered conserved, if the target gene is also the first gene in an operon.
However, the genes targeted by several different siRNAs were found to be more weakly conserved than the target genes on average (Additional file 7).
It is obvious that the TF itself has to be conserved in the target organism; but the second condition (homologous target genes) is very important as well to provide reliable, high-quality predictions since a high-scoring PWM-based sequence match alone is not very meaningful [ 10].
It was also noted that a GCATTA query (i.e. the complement of hsa-miR-155 residues 2-7) resulted in a minimal enrichment score of 30, indicating that the first residue position is highly conserved in the target transcript 3'UTRs (not shown).
To account for errors in the alignment of orthologous 3'-UTRs, we counted as conserved the same miRNA target site found within 50 bp of each other across species.
As a second approach, we randomly permuted (scrambled) the target sequence found in each interaction, while conserving the nucleotide content of the targets.
We consider a regulation as evolutionarily conserved, if in the target organism (1) the transcription factor is conserved, (2) the target gene is conserved and (3) the target gene possesses the binding site for the transcription factor in its upstream region.
However, if there is a selective pressure to conserve a target site, the distribution will be shifted to the right.
