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In #325/#339, an attempt was made to add support for limma mixed models. However, I believe this approach is not ideal for the following reasons
Limma supports only one random effect variable
It requires to manually combine multiple experimental factors into a single variable, therefore making it cumbersome to use
Alternatively, I propose to add support for a linear mixed effects model that generalizes to an arbitrary number of random effects and allows to specify random effect variables using Wilkinson formulas, e.g. ~ timepoint + (1 | patient_id).
An obvious candidate would be DREAM which is a generalization of limma/voom for random effects. It's certainly a good choice for gene expression data as it also does the empirical bayes shrinkage of gene dispersions.
However, there's also other models that could be condidered, e.g. MRMM, or plain lme4 models.
Depends on #362 for the Wilkinson formulae
Mixed effects models are also a way of addressing technical replicates -> fixes #220
@nschcolnicov@atrigila@grst@apeltzer The basic module and a preliminary position within the workflow is completed. I'll work on defining some parameters that can be used to customize the modeling in Dream (like limma and deseq2). Later, we need to update the yml structure to decide how/when to call this module with the formula/contrasts definition. I think it can be used in parallel with deseq2 when there's no random variables associated as well. Just to open debate
grst
changed the title
Support for linear mixed effects models
Support for linear mixed effects models via DREAM
Jan 10, 2025
Description of feature
In #325/#339, an attempt was made to add support for limma mixed models. However, I believe this approach is not ideal for the following reasons
Alternatively, I propose to add support for a linear mixed effects model that generalizes to an arbitrary number of random effects and allows to specify random effect variables using Wilkinson formulas, e.g.
~ timepoint + (1 | patient_id)
.An obvious candidate would be DREAM which is a generalization of limma/voom for random effects. It's certainly a good choice for gene expression data as it also does the empirical bayes shrinkage of gene dispersions.
However, there's also other models that could be condidered, e.g. MRMM, or plain lme4 models.
Depends on #362 for the Wilkinson formulae
Mixed effects models are also a way of addressing technical replicates -> fixes #220
CC @apeltzer @tschwarzl @nschcolnicov @atrigila @alanmmobbs93
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