How to get results from random intercepts using the limma package?
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@macsuejacques-24257
Last seen 3.3 years ago

Hello,

I have a question in relation to limma and how to extract the random intercepts results after running a duplicated correlation. To summarize, I have DNA methylation data from a repeated intervention that was inter-spaced by one year of wash out. What I would like to see is if DNA methylation markers change similarly even after one year of wash out when the same intervention is applied again. My code is as follows:

design=model.matrix(~intervention+Age+Batch,data=pheno) 

library(limma)

corfit <- duplicateCorrelation(DMFS,design,block=pheno$ID)

fit = lmFit(DMFS, design,maxit=1000,block=pheno$ID,correlation=corfit$consensus) 

fit2 <- eBayes(fit)

Where the outcome is delta DNA methylation (Delta M-values), intervention is 1 or 2. Then n the duplicateCorrelation I have blocked by participants ID (random intercept). However I can seem to find a way to extract results from this random intercept. I would like to see if any CpGs (probes) change similarly in both interventions, at the individual level. Thus I need estimate, SD and p-values for the random intercept. Can anyone help please?

limma • 1.4k views
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Hi, you should have mentioned that you have also posted on Biostars ( https://www.biostars.org/p/464605/ ). Thank you.

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Oh I apologize, I didn't realize those were linked. I will avoid this in the future. It is my first post for help.

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No problem. It just helps us to know whether or not the question has already been answered elsewhere

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@gordon-smyth
Last seen 2 hours ago
WEHI, Melbourne, Australia

First, I need to point out that duplicateCorrelation fits a mixed linear model random effect. A "random intercept" is something different that is not needed in the limma context.

Sorry, but you are asking for things that don't exist. Random effects don't produce p-values. It just isn't mathematically meaningful to include participant as a random effect but also try to test for differential methylation for individual participants. Testing for results at the individual level is also not a normal thing to do from a scientific point of view.

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Hello Gordon,

Firstly thank you for your answer. Maybe I wasn't clear in my question.

What I would like is to get results from the random component of the model. Is there a way to test whether the random effects are significant? That is something that mathematically exists, as far as I know. It's implemented in the lmerTest package, by testing the fit of a model with and a model without random effects.

Also I don't understand why you say you can't test for results at the individual level from a scientific point of view. If you have multiple observations per individual, you should be able to get a sense of the within-subject variability and hence, compare individuals with each other in their trainability (i.e. consistent response) no?

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duplicateCorrelation fits a global model to estimate a common intrablock correlation across all genes. So the concept of doing genewise tests for the random effect doesn't exist.

If you want to test for differences between participants (equivalent to testing the variance component for participants equal to zero) just add participant to the design matrix instead of as a block.

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