[miso-users] Accounting for batch effects

[Yarden Katz]

Hi Larry,

The problem of batch effects is very similar to the problem of modeling variability within biological replicates.  MISO currently doesn't have a built-in solution for that.  See this (http://genes.mit.edu/burgelab/miso/docs/#answer13) for a discussion of the issue and how to deal with it outside of MISO.

We're working on modeling this problem, but in the meantime the ways to address it are discussed in the link above. For what it's worth, the Psi quantity is internally normalized.  It doesn't mean that it will not suffer potentially from batch effects, but (anecdotally) we've found that this quantity suffers less from batch effects compared with RPKM or units of gene expression which will be more sensitive to the composition of the RNA, etc. -- although gene expression values are certainly easier overall to estimate reliably than Psi values.  Again, I'm sure batch effects can creep in, but they're less obvious in this context.  

In any case, it's worth seeing what the extent of the batch effects are and whether they can be normalized as a post-processing step.  We're working on native probabilistic models for this but I imagine that the right solution will depend on the kind of batch effects and variability in your experiment, and a generic solution that fits all experimental design is in my view unlikely.

Best, --Yarden

On Jul 25, 2013, at 5:25 PM, Singh, Larry (NIH/NHGRI) [E] wrote:

> Dear MISO users,
> 
> I'm new to MISO, but would like to use it for differential expression and eQTL analyses of a large number of samples.  Initial analyses have shown though that there are likely batch effects.  Is there a method in MISO for accounting for batch effects?  I've searched the web and the miso-users archives and couldn't find an answer.
> 
> Thank you kindly for your attention.
> -Larry.
> 
> --
> Larry N. Singh, Ph.D.
> Research Fellow
> Genetic Diseases Research Branch
> National Human Genome Research Institute, NIH
> Building 49, Room 4A52
> 49 Convent Dr., Bethesda, MD 20892-8004
> (301) 451-4699
> 
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