Hi, I am new to bioinformatics. I use EdgeR. I analyze a study in humans with 3 factors, each having about 5 levels. Can this pose a problem for modeling for differential analysis? Can explicatives variables be added to the model? Thank you for your help.

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edgeR handles any number of factors and levels. That's no trouble at all from a software point of view but, naturally, the more effects and coefficients you want to estimate, the more data (samples) you need to have.