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Because the only available conservation data for human are at Galaxy [47], and because they also include information for rhesus and mouse, we used the human miRNA genes to calculate the conservation scores for the NRdmiRs, PRdmiRs and RdmiRs.

For mouse, we used the same criterion as in Johnston et al. [ 21] to consider qualified genes.

To compute the correlation between posterior probabilities of TSS association in human and mouse, we used the following procedure.

To perform germline mutagenesis of the NOD mouse, we used two SB constructs previously used in mice.

For mouse, we used the conservation scores generated by alignment of 30 vertebrate genomes to the mouse genome (mm9 assembly).

To score a specific reference MLV as present in a mouse, we used a strict criterion of 100%% identity between a sequence read and the reference sequence.

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For mouse, we use the MouseFunc benchmark (Pena-Castillo et al., 2008), which consists of 10 networks and covers 21 603 mouse genes.

The Rgs5 gfp/ + mouse we use is a knock-out/knock-in mouse and is retaining the full promoter region [ 39].

Regarding the effects of GO on mice, we used tail vein injection pathway to evaluate the in vivo toxicity.

Regarding the effects of FMNPs on lifespan of mice, we used tail vein injection pathway to evaluate the in vivo toxicity of FMNPs.

To identify conserved intronic sequences expressed in both humans and mice, we used custom-designed human cDNA microarrays to separately interrogate RNA from mouse and human liver, kidney, and prostate tissues.

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