[BioC] Combining replicate spots in CGH data

[Ramon Diaz-Uriarte]

On Wednesday 06 December 2006 17:12, João Fadista wrote:
> Dear all,
>
> I was wondering if there are other methods for combining replicate spots
> other than the average or the median. I am asking this in concern with CGH
> data analysis because I do not know how, and if, we can take advantage of
> the genomic structure of the array CGH data for combining replicate spots.
>
> For the sake of the argument I put below two hypothetical examples:
> - Combining replicate spots in a different way depending on what region of
> the chromosome or genome they are; - Or give more weight to spots that we
> know that have more reliability.
>
> Something like this if you know what I mean.



Dear Joao,

This is nothing ellaborate; just a couple of thoughts.

1. I assume you mean true replicate spots. In other words, these are the exact 
same DNA piece, and they map to exactly the same locations in the chromosome.

2. Ideally, I'd like a method that can deal with replicate spots without even 
asking you to take the mean or the median. One problem I find with means or 
medians is that, if you do not have the exact same number of replicates for 
all locations, then you are estimating a value that has different variances 
over different locations.

I think (non-homogeneous) HMMs and related techniques are suited for dealing 
with arbitrary (and different) number of replicate spots: at location "t" you 
happen to have more than one observation, and you are fitting a model where 
those observed log ratios come from an emission function, blablabla. By not 
taking means/medians/whatever, you do not violate assumptions related to the 
variance of the emission functions. In other words, conditional on being on 
state "k" you are log ratios are, say, ~ N(mu, sigma). 


(I'll admit we have a "hidden agenda", with our RJaCGH package :-).

R.

>
>
> Best regards
>
> João Fadista
> Ph.d. student
>
>
>
>  	 Danish Institute of Agricultural Sciences
> Research Centre Foulum
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-- 
Ramón Díaz-Uriarte
Bioinformatics 
Centro Nacional de Investigaciones Oncológicas (CNIO)
(Spanish National Cancer Center)
Melchor Fernández Almagro, 3
28029 Madrid (Spain)
Fax: +-34-91-224-6972
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