THANK YOU FOR HELPING ME There are 23221 human proteins with some Gene Ontology
ID: 62891 • Letter: T
Question
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There are 23221 human proteins with some Gene Ontology (GO biological process annotation. You conduct a gene expression microarray experiment and identify 443 genes that are up-regulated; you can assume that the remaining 22778 (23221 – 443) genes are not up-regulated. Using GO, you note that 52 of the up-regulated genes are annotated as participating in the “Notch signaling pathway”. There are a total of 120 proteins in GO annotated with the term “Notch signaling pathway”.
1. Without using a calculator or computer, do you think you have an enrichment of Notch signaling pathway members in your list of up-regulated genes? Describe your intuition for why there is or isn’t enrichment of the GO term in your list. Hint: think in terms of percentages.
2. Fill out a contingency table that describes the overlap between up-regulated genes and “Notch signaling pathway” annotated genes. What distribution can be used to calculate the probability of observing this contingency table? Set up the formula and enter the correct numbers for calculating the probability, but DO NOT compute the probability.
3. How many contingency tables would be required to calculate a p-value for assessing significant enrichment of the Notch signaling pathway in your list of up-regulated genes? Note that the maximum number of genes that can be both up-regulated and belong to the Notch signaling pathway is 120.
4. Go to http://www.langsrud.com/fisher.htm and calculate the p-value (use right sided). Is finding 52 Notch signaling pathway proteins in a list of 443 upregulated genes significant? Explain and cite the appropriate numbers.
Explanation / Answer
1. yes, there is an enrichment of notch signalling pathway members in up-regulated genes. Total 443 genes are up-regulated (highly expressed). Out of these 52 genes are annotated as participating in the “Notch signaling pathway”. i.e. about 10 % genes.
There are a total of 120 proteins in GO annotated with the term “Notch signaling pathway (120-52=68 ). 68*100/ 22778 % down-regulated genes participate in notch signalling. This number is very less in comparison to that present in up-regulated genes. So, we can say that notch signalling pathway members are present in more quantity in up-regulated genes. Up-regulated genes are those which are highly expressed, so is notch signalling pathway which is highly conserved.
Down regulated genes are less expressed; and will be less conserved; so, they have less number of notch-signalling pathway members.
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