Tissue Specific Mirna Microarray Results

Question

[Assa Yeroslaviz]

Hello everybody,

I know this question can be found here in different versions, but I need to ask it again, as I cold not find the right answer for my problem.

I have a set of miRNA microarrays for four different tissues. I would like to know if there a way of comparing them to define tissue-specificity for certain miRNAs.

The biologist who gave me the data wanted a comparison of all four tissues. The definition of specificity was than for a miRNA to have a stronger expression intensity of at least 15% higher than all other three tissues.

I know that the method of defining specificity in this way is relatively arbitrary, but I would like to ask if the method we're using is acceptable.

I have the feeling that 15% is very low difference, but I couldn't find any literature to back me up on this. Does anyone know if there are any papers to this kind of a problem?

Is there. A better way to define miRNA tissue specificity?

Answer 1

[Sean Davis]

I would suggest using a microarray analysis software to define the differences statistically. There are many such packages, so try checking at your institution to see what commercial software is available. Alternatively, there are many free alternatives (I am partial to the limma package from the bioconductor project). Using a statistical test reduces both your false positive and false negative rates, assuming that you have a few replicates for each tissue.

Answer 2

[Larry_Parnell]

I don't have access to my data and the references therein at the moment. Much of the expression data I have collected (from published sources), both for mRNAs and miRNAs, uses metrics like FDR to assess significant differential expression. If FDR is low, then a 10% change in expression can be significant, and trustworthy for building an explanation and further hypotheses. Much of the data I have use FDR or similar approaches and show changes in expression from control of +/- 10-15% and higher. So, 15% can be fine if the change has low FDR or is significant or low variance.

Answer 3

[Andrew Su]

The other two answers here are good in that they talk about ways to get statistical significance, but I'm not sure they really address the "tissue-specificity" question you're asking. First off, defining "specificity" based on a survey of four tissues seems pretty tenuous to me (though it sounds like you're aware of this). And you're right, anything thresholds you choose will be rather arbitrary, so ideally they are chosen with an eye to how the results will be used (tolerance to false positives and false negatives).

If your primary interest is in using criteria that are defensible relative to a published study, you could reference our previous paper here. But wow, talk about rudimentary criteria -- almost painful to look at now.

[Assa Yeroslaviz]

thanks for that paper. The way you descirbe in your paper is basically what I planned to do. Though I am not sure if 100% higher AD is not too much. As Larry said in the previous answer, there are some approaches which show expression changes of 15%. maybe the arrays are now more sensitive than 2002.

[Assa Yeroslaviz]

Does anyone know about papers where they describe changes in this low region?