Pathway

Question 1

Pathway analysis

Answer 1

associating genes with pathway. pathway represent what we know of the function of the gene. many genes we dont know to which pathway they belong

used to perform a study and have biologist make a list of genes they see being related but this is biased on the biologist knowledge and interpretation

use over representation that is a mathematical method to remove the bias

Question 2

Over representation

Answer 2

Have a list of differentially expressed genes
and a list of genes from the pathway
Check the overlap of the differentially expressed genes with the genes from the pathway. Then see if this overlap is larger than would be expected by chance.
Give as output significantly associated genes with the pathway
Use the formula from the appendix !
( a ; b) = a!/b!(a-b)!

drawback: need to have a differentiated list that we obtained through statistical test and then all the variables are treated equally

Question 3

Background list

Answer 3

important to compute the pathway significance with full background list otherwise it can skew the results => become less significant

Question 4

Mapping

Answer 4

Mapping are done with the identifiers and the database
a same identifier is linked to many genes. make sure to first convert to the identifiers then only perform the significant genes otherwise this will completely change the results !

Question 5

Enrichment

Answer 5

Doesnt use a background list
takes a value for each element measured

Set Enrichment Analysis
Wilcoxon Enrichment
Kolmogorov Smirnov test

Question 6

Set Enrichment Analysis

Answer 6

Order the list of elements by their values: correlation or absolute value of change or something else

Look for pathway by looking at elements bunched together
1st gene in pathway ? no ? score -1 Yes ? Score +1
Is 2nd genre in pathway ? and so on
Score for being in pathway usually larger than a miss

p values computed by repeating permutations

Criticism: if no change in the pathway then will be at the bottom of the list clustered together. Weight the score to avoid this.

Question 7

Wilcoxon Enrichment

Answer 7

Pathway affected have either most genes expression increased or dicreased. Test if this is the case

Question 8

Kolmogorov Smirnov test

Answer 8

Check if the cumulative distribution of the pathway genes and the entire set of genes is similar
compare and take biggest difference

Question 9

Gene ontology

Answer 9

Description for genes
Do 3 trees
Biological process and molecular function : what it does
cellular compartment

associate genes with these terms on the trees

The pathway algorithms can also be used to find the interesting gene encology terms
significant should be linked