[miso-users] Accounting for batch effects

[Singh, Larry (NIH/NHGRI) [E]]

Hi Yarden,

Thanks very much for your response.  This may be a naïve question, but
what about using normalized read counts to start with.  For instance,
instead of computing PSI_MISO with read counts, use RPKM (FPKM) instead.
I haven't read the methods in your paper completely, so I apologize if
this suggestion makes sense. :)

Thanks again for getting back to me so promptly.

Regards,
-Larry.

On 7/25/13 8:02 PM, "Yarden Katz" <yarden at mit.edu> wrote:

>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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