Introduction to pathway enrichment analysis Flashcards
1
Q
What happens once you receive a “hit” from a screen?
A
- Genomics and proteomics study
- Gather information about their enrichment in known pathways, complexes, functions
2
Q
Explain
Pathway and Network Analysis
A
- Any analysis involving pathway or network information
- Most commonly applied to interpret gene lists
- Most popular is pathway enrichment analysis
- Helps gain mechanistic insight into omics data
3
Q
Define
Pathway
A
- Detailed, high-confidence consensus
- Biochemical reactions
- Small-scale, fewer genes
- Made from decades of literature
4
Q
Define
Network
A
- Simplified cellular logic; noisy
- Large-scale, genome wide
- Constructed from omics data integration
5
Q
What are the benefits of pathway data (vs. transcripts, proteins, SNPs)?
A
- Improves statistical power (fewer tests)
- More reproducible (gene expression signatures)
- Easier to interpret
- Identifies mechanisms
- Predicts new roles to genes by association
6
Q
What is the workflow of pathway analysis?
A
- Collect genomics data
- Normalize and score (compute differential expression)
- Generate gene list
- Learn about underlying cellular mechanism using pathway and network analysis
7
Q
Define
Gene lists
A
- Biological system: complex, pathway, physical interactors
- Similar gene function
- Similar cell or tissue location
- Chromosomal location
8
Q
How to identify genes and proteins?
A
- IDs are unique, stable names or numbers
- Important to recognize the correct record type (gene, protein, RNA)
9
Q
What are the main uses of identifier mapping?
A
- Searching for a gene name
- Link to related resources
- Identifier translation (proteins to genes)
- Merging data from different sources
10
Q
What are some other annotations that can be added?
A
- GO terms for molecular function, cell location
- Chromosome position
- Disease association
- DNA, transcript, protein properties
- Interactions with other genes
11
Q
Describe
Annotation sources
A
- Manual annotation by scientists (high quality, time-consuming)
- Electronic annotation (variable accuracy, lower quality)
12
Q
What are the types of pathway/network analysis?
A
- Enrichment of fixed gene sets (what biological processes are altered in this cancer)
- De novo sub-network construction/clustering (are new pathways altered in this cancer)
- Pathway-based modeling (how are pathway activities altered in a particular patient)
13
Q
Advantages/Disadvantages
Enrichment of fixed gene sets
A
- Easy to perform, good tools, good statistical model
- Many possible gene sets, lots of overlap
- Bags of genes that obscure regulatory relationships
MOST POPULAR
14
Q
Explain the two-class design for gene lists
A
Expression matrix (Cases vs Controls) either becomes
* Genes ranked by differential statistic
* Selection by threshold
15
Q
How to perform a gene list enrichment test?
A
- Defing gene list and background list
- Select gene sets (pathways) to test for enrichment
- Run enrichment tests (w/ Bonferroni/Benjamini-Hochberg corrections)
- Interpret enrichments
