Hi Gordon,
some good points you make here.

I have checked back to the original slide and there was a background smear
over one corner covering an entire print tip region, so a researcher would
have subjectively flagged all those spots as bad, which is why they were
all allocated zero weight. For global loess normalization such as with
agilent arrays, a researcher would also potentially remove the entire
biological replicate from analysis.

I am tending towards the solution should also be NA for the situation
above. Maybe a conditional switch could be used to cover the options,
ordinary unweighted normalization, and doing no normalization etc for
historical/backward compatability reasons.

Marcus


On Wed, Sep 5, 2012 at 11:21 AM, Gordon K Smyth <smyth@wehi.edu.au> wrote:

> Hi Marcus,
>
> I guess the fundamental question then is, what should loess normalization
> return (for a array or print-tip group or whatever) when all the weights
> are zero?
>
> Strict mathematics would suggest that the solution should be NA.
>
> Practical considerations suggest to me that normalizeWithinArrays() might
> be better performing ordinary unweighted loess normalization in this case,
> because no probe is weighted as more reliable than any other.
>
> Or alternatively, one might say that the loess curve can't be estimated,
> so the raw expression values should be returned without adjustment.  So
> loess normalization with zero weights is equivalent to no normalization.
> That is what loessFit() and normalizeWithinArrays() have been doing up to R
> 2.14.1.
>
> If you make the weights all zero for a print tip, do you want
> normalizeWithinArrays to return NAs for all probes in that print tip group
> on that array?  Or do ordinary unweighted normalization?  Or do no
> normalization?
>
> Regards
> Gordon
>
>
> On Wed, 5 Sep 2012, Marcus Davy wrote:
>
>  It looks like this error is related to a particular print tip having all
>> weights=0 as input into stats:::simpleLoess. I am trying to construct a
>> simple reproducible example.
>>
>> Marcus
>>
>
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