[BioC] pathway score for individual arrays

Saroj K Mohapatra saroj at vt.edu
Thu Jun 4 23:59:33 CEST 2009


Hello Guido:

I am just curious how combining gene expression measurement into a 
gene-set measurement ("pathway score") would affect the downstream 
statistical tests, if any, to be later performed on these scores.

For example, in case of simple GSEA [1]: (a) per-gene t-statistics have 
a t-distribution, and (b) assuming observed t-statistics are 
independent. Combined these two lead to: sum of t-statistics taken over 
genes in a gene set divided by the square root of number of genes should 
have approximately normal distribution. This property can then be used 
to find outliers (interesting pathways).

I wonder if there is anything similar for gene expression measurements?

Best wishes,

Saroj

[1] Section 13.1.1. of Chapter 13 of Bioconductor case studies by Hahne 
et al (Springer) pp.194-195


Hooiveld, Guido wrote:
> Dear list,
>  
> Although not directly related to BioC, I would appreciate any pointer to
> papers/methodology related to the question of how to calculate a pathway
> score (for e.g. pathways defined by KEGG) for an individual array.
>  
> TIA,
> Guido
>  
> Background: we standardly use methodology like GSEA to find pathways
> that are regulated upon treatment compared to control. For example, GSEA
> calculates a 'pathway score' (the Normalzed Enrichment Score NES) by
> combining and comparing expression data from all replicates from an
> experimental and control groups. We now would like to calculate a
> pathway score for each individual array (thus like having an expression
> estimate per array for a probeset, but now for a pathway), but i don't
> know how to approach this.
>
> ------------------------------------------------ 
> Guido Hooiveld, PhD 
> Nutrition, Metabolism & Genomics Group 
> Division of Human Nutrition 
> Wageningen University 
> Biotechnion, Bomenweg 2 
> NL-6703 HD Wageningen 
> the Netherlands 
> tel: (+)31 317 485788 
> fax: (+)31 317 483342 
> internet:   http://nutrigene.4t.com <http://nutrigene.4t.com/>  
> email:      guido.hooiveld at wur.nl 
>
>
>
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