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For these analyses, we enforced very stringent settings for "ease" (Ease = 0.00001), P-value (≤ 0.00001), and "false discovery rate" (≤ 0.01) together with a minimum fold enrichment of 1.7.
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Such genomic regions were further filtered to include sequences with minimum 1.3 fold enrichment, and minimum −1.3 fold depletion.
GREAT figures were produced with an in-house R tool and are ranked according to the same default criteria used by the GREAT (binomial FDR q-value is ≤0.05 with a significant hypergeometric FDR q-value and a minimum region fold enrichment of 2).
Indicated is fold enrichment (fold enrich) and the corresponding one-sided Fisher's exact test (FET) P value.
The GO terms "cell division", "cell death", "cell migration", "cell cycle", "mitotic cell cycle" and "cell proliferation" displayed a fold enrichment of at least 6.27 for zebrafish and 6.5 for newt with a minimum of 13 proteins annotated for zebrafish and 61 proteins annotated for newt.
Thresholds for the matching score were further adjusted to a minimum of 2-fold enrichment of motif abundance either in the group of non-responsive genes or responsive genes.
In order to select the most relevant binding sites, we selected peaks with a minimum of two-fold enrichment over IgG control and large area, which correlated with peak height in a linear fashion (Supplementary Figure S1A).
Among the total 2,807 intermediators, 230 (Supplementary Table S3) met our significance criteria: having at least five interacting drugs via their targets, a BH-corrected P value < 0.05, and a minimum of 1.5-fold enrichment of drug-degree in the DIPN networks compared with the average drug-degrees of the random networks.
The fold enrichment was detected by qPCR.
Relative fold enrichment presented enrichment of 5mC on TFPI2 promoter: relative fold enrichment = 2 input Ct − sample Ct)/2 input Ct – IgG Ct).
The top 30 terms ranked according to fold enrichment are shown.
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