Peter, Chuck,

Big thanks for your input.

I will be following up each and every of your suggestions on the morrow.

Something of note though that you may have further thoughts on- phyper() was *specifically* recommneded by BioC responders for my application in spite of the fact i originally thought a bootstrapping approach seemed most logical given a quasi dependency* between gene lists. I implore you to have a thorough read through my recent BioC thread here:

http://permalink.gmane.org/gmane.science.biology.informatics.conductor/27909

After more than a week since posting on the BioC without response, i reposted here the question you now kindly addressed. Clearly i'm yet to resolve this by following up your suggestions, and any response you may offer on the BioC thread will no doubt be enlightening for me.

Thanks again,

Karl

*Probably gene expression has varying levels of dependancy, but atleast for comparing the 3 lists i can say they all come from independent biological replicates (animals) which in theory doesn't violate any of phypers assumptions. Right? I won't go into my 2 gene-list comparisons which are between 'paired' tissues each derived from the same animals. They probably can not be considered truly independant...



On 3/30/2010 7:04 PM, Peter Ehlers wrote:
Karl,

I strongly support Chuck's recommendations.
If you do still want to compute such probabilities 'by hand',
you could consider the lchoose() function which does work
for your example.

-Peter Ehlers

On 2010-03-30 9:55, Charles C. Berry wrote:
On Tue, 30 Mar 2010, Karl Brand wrote:

Dear R Users,

I employed the phyper() function to estimate the likelihood that the
number of genes overlapping between 2 different lists of genes is due
to chance. This appears to work appropriately.

Now i want to try this with 3 lists of genes which phyper() does not
appear to support.

Some googling suggests i can utilize the Multivariate hypergeometric
distribution to achieve this. eg.:

http://en.wikipedia.org/wiki/Hypergeometric_distribution

But when i try to do this manually using the choose() function (see
attempt below example with just two gene lists) i'm unable to perform
the calculations- the numbers hit infinity before getting an answer.

Searching cran archives for "Multivariate hypergeometric" show this
term in the vignettes of package's ‘combinat’ and ‘forward’. But i'm
unable to make sense of the these pachakege functions in the context
of my aforementioned apllication.

Can some one suggest a function, script or method to achieve my goal
of estimating the likelyhood of overlap between 3 lists of genes,
ideally using the multivariate hypergeometric, or anything else for
that matter?


Two suggestions:

1) Don't! Likely the theory is unsuited for the application. In
most applications that generate lists of genes, the genes are
not iid realizations and the hypergeometric gives results that
are astonishingly anticonservative. As an alternative , the
block bootstrap may be suitable. See
http://171.66.122.45/cgi/content/abstract/17/6/760

and Google (scholar) 'genomic "block bootstrap"' for some
starting points.


2) Take this thread to the bioconductor list. You are much
more likely to get pointers to useful packages and functions
for genomic statistical software there.

HTH,

Chuck



cheers in advance,

Karl



#example attempt with two gene lists m & n
N <- 45101 # total number balls in urn
m <- 720 # number of 'white' or 'special' balls in urn, aka 'success'
n <- 801 # number balls drawn or number of samples
k <- 40 # number of 'white' or 'special' balls DRAWN

a <- choose(m,k)
b <- choose((N-m),(n-k))
z <- choose(N,n)
prK <- (a*b)/z #'the answer'
print(prK)
[1] NaN

a
[1] 7.985852e+65
b
[1] Inf
z
[1] Inf


--
Karl Brand
Department of Genetics
Erasmus MC
Dr Molewaterplein 50
3015 GE Rotterdam
T +31 (0)10 704 3457 | F +31 (0)10 704 4743 | M +31 (0)642 777 268

______________________________________________
R-help@r-project.org mailing list
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PLEASE do read the posting guide
http://www.R-project.org/posting-guide.html
and provide commented, minimal, self-contained, reproducible code.


Charles C. Berry (858) 534-2098
Dept of Family/Preventive Medicine
E mailto:cbe...@tajo.ucsd.edu UC San Diego
http://famprevmed.ucsd.edu/faculty/cberry/ La Jolla, San Diego 92093-0901



______________________________________________
R-help@r-project.org mailing list
https://stat.ethz.ch/mailman/listinfo/r-help
PLEASE do read the posting guide
http://www.R-project.org/posting-guide.html
and provide commented, minimal, self-contained, reproducible code.


--
Karl Brand
Department of Genetics
Erasmus MC
Dr Molewaterplein 50
3015 GE Rotterdam
T +31 (0)10 704 3457 |F +31 (0)10 704 4743 |M +31 (0)642 777 268

______________________________________________
R-help@r-project.org mailing list
https://stat.ethz.ch/mailman/listinfo/r-help
PLEASE do read the posting guide http://www.R-project.org/posting-guide.html
and provide commented, minimal, self-contained, reproducible code.

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