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use of IEP evidence code example paper PMID:21993888
Two microRNAs, miR-330 and miR-125b-5p, mark the juxtaglomerular cell and balance its smooth muscle phenotype
Differentially expressed miRNAs after the reacquisition of the renin phenotype are shown in Table 1 and as heat maps in Fig. 1, A and B. This analysis identified a total of 48 miRNAs differentially expressed in SMCs that had been induced to acquire the renin character (Fig. 1A). Twenty-two miRNAs were upregulated, and 26 were downregulated. In the kidney cortex, four miRNAs were differentially expressed after reacquisition of the renin phenotype (1 upregulated and 3 downregulated, Fig. 1B).
My review of this paper below and the evidence codes I would have used:
In vitro studies: vascular SMCs of the renin lineage cells permanently labeled with CFP (a marker of cells of the renin lineage) and express renin upon stimulation with cAMP: This analysis identified a total of 48 miRNAs differentially expressed in SMCs that had been induced to acquire the renin character (Fig. 1A). Twenty-two miRNAs were upregulated, and 26 were down regulated. Annotation of 48 different miRNAs cellular response to inorganic substance IEP (these have the IDA evidence code in MGI).
In vivo studies: To induce reacquisition of the renin phenotype in kidney cortex cells of the renin lineage in vivo, mice were administered a low-sodium diet (0.05%, Harlan, Madison, WI) plus captopril (Sigma, St. Louis, MO) in the drinking water (0.5 g/l) for 10 days. In the kidney cortex, four miRNAs were differentially expressed after reacquisition of the renin phenotype (1 upregulated and 3 downregulated, Fig. 1B) Annotation of 4 different miRNAs cellular response to inorganic substance IEP (these have the IDA evidence code in MGI).
There were 6 IDA annotations associated with this paper, based on Figure 4B and associated with mir125b-1, mir125b-2 and mir330, which I think are using the correct evidence code: All 3 miRs IDs are associated with juxtaglomerular apparatus development IDA mir125b-1, mir125b-2 are associated with positive regulation of gene expression IDA mir330 is associated with negative regulation of gene expression IDA
These are based on the data in Figure 4B which shows the effects of miR-330, miR-125b-5p or their inhibitors on the expression of Smtn. Transfection of SMCs with pre-miR-330 reduced Smtn expression compared to controls. miR-330 inhibitor had no effect on Smtn expression. Whereas, transfection with pre-miR-125b-5p increased Smtn expression. miR-125b-5p inhibition reduced Smtn. These results suggest that miR-330 inhibits and miR-125b-5p promotes the smooth muscle phenotype of renin cells.
I would therefore like to raise an instance of an experiment where a change in miR expression levels, following a change in cell state, should not be annotated as IDA, such as the one above, if you agree that the evidence code here should be IEP and not IDA. To be honest I think the miR community would like to have the information that could be captured by the application of IEP, simply because there is so little verified annotation data available. However, possibly this could be left to other resources to provide.