

Hello all,

I work for an in vitro diagnostic company and we are interested in
analysing microarray gene expression data, we try to identify molecular
signature to discriminate two populations (healthy and Cancer) .

We have collected 100 samples and hybridized them with a given protocol
and have identified a molecular signature based on these data.

We then plan to assess the performance of such a signature, so we collect
100 new samples and have hybridized with an "upgrade" version of the first
protocol.

According to biologist there is no big difference between the two
protocols.

But when comparing the two populations (first and second protocol) with
classical exploration technics (MDS, PCA) we can see that there is a clear
difference between the two series.

I try to explain to biologist that the two series are quite different and
normalizing the data will not solve the problem of changing protocol and
explain them consequently it's not a problem of normalization.

I proposed to the biologists to take few samples and to hybridize them
(same samples) with the two protocols to try to see if there can be a
relationship explaining the difference between the two protocols, so that
each sample will be hybridized with the two protocols.

My questions are :

How to best analyse these 10 samples (5*2)?

Is there a way to try to make the two populations comparable (I tried to
normalize the data with quantiles and invariant set but we still have the
two groups) ?

Is it reasonable to combine the two series to try to identify a new
signature ?

Any help will be greatly appreciated,

Thanks in advance,

Malick,

Malick Paye | bioMérieux | Biomathematician
Phone: (+33)4 78 87 70 97 | Fax: (+33)4 78 87 53 40
[Parc Polytec, 5 Rue des Berges, 38004 Cedex 01  Grenoble, France]


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