Functional Annotation of Biological Networks

Question 1

Define

Biological networks

Answer 1

They represent a type of connection between a type of biological components

Question 2

What are the pros and cons of biological networks?

Answer 2

• Good interpretation for individual interactions, local structures/modules
• Much worse understanding of global organization and meaning (hairballs)

Question 3

Define

Genetic interaction

Answer 3

• A functional relationship between two genes revealed by the fact that the double mutant has an unexpected phenotype
• Ex: synthetic lethality is negative and epistatis is positive

Question 4

How to perform

S.A.F.E.

Answer 4

Spatial Analysis of Functional Enrichment
1. Take a node A in network
2. Find all other nodes B that can be reached by travelling a distance less or equal to d
3. Determine if nodes B are statistically enriched for a functional attribute
4. Associate A with the -log10 of the enrichment p-value
5. Repeat for all other nodes in the network

Question 5

Define

Gene ontology

Answer 5

• Attempt to organize information about biological processes, molecular functions of cellular compartments
• Built as a set of hierarchical terms

Question 6

How to build a composite enrichment landscape?

Answer 6

Combine all enrichment landscapes and calculate a weighted sum of color intensities

Question 7

Describe

The SAFE-based annotation of the GI network

Answer 7

• Every label: the top 5 most frequent words in the names of the GO terms
• Every color: a group of GO terms enriched in that region

Question 8

How to estimate the robustness of SAFE?

Answer 8

• Are the domains identified by SAFE similar to manual network annotations?
• How critical is the value of d?
• Are enrichment landscapes consistent across different network layout runs?
• How important is the quality of the functonal annotation standard? Is SAFE sensitive to false positives/negatives

Question 9

Why is SAFE sensitive to signal and robust to noise?

Answer 9

• It identifies all manually annotated regions + 3 more
• Robust to sources of variation (layout runs, distance parameters, annotation errors)
• Fast and automated

Question 10

What is S.A.F.E. useful for?

Answer 10

• It recapitulates known modes-of-actions of chemical compounds
• SAFE uncovers potentially new mechanisms of drug activity

Question 11

What are the questions answered by SAFE?

Answer 11

• Are any regions of the network specifically associated with a given function or phenotype?
• Where in the network are these regions localized?
• How does their localization compare to that of other functions or phenotypes?

The result is a functional map of the network and enables the investigation of inter-process relationships