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Cory Tobin. An Exploratory Method to Reconstruct Pathways. Collaborators. Dr. Matteo Pellegrini Shawn Cokus @ UCLA. Outline. Purpose Methods Sample Data Possible Uses Final Remarks. Purpose.

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Presentation Transcript
collaborators
Collaborators

Dr. Matteo Pellegrini

Shawn Cokus

@ UCLA

outline
Outline
  • Purpose
  • Methods
  • Sample Data
  • Possible Uses
  • Final Remarks
purpose
Purpose

Reconstruct signal transduction pathways & protein complexes using protein-protein interactions reported on the web

materials
Materials
  • Python
  • Yahoo! Search API
  • ProstgreSQL
  • Django Web Framework
methods
Methods

Construct high likelihood / low noise queries

Ex: “Jak2 phophorylates Stat5”

Query Yahoo! for every permutation of 2 proteins in a given species

Use high likelihood joining words…

joining words
Joining Words

Phosphorylates

Methylates

Acetylates

Activates

Deactivates

Binds to

Inhibits

Dephosphorylates

Glycosylates

Ubiquitinates

Interacts with

full query
Full Query

“Jak2 acetylates OR phosphorylates OR methylates OR binds to OR interacts with Stat5”

hindrance
Hindrance

Doing pair-wise queries for all N proteins in an organism requires N*N queries

E. coli has >4000 genes

(16,000,000 queries)

Yahoo! allows 5k / day / computer

possible solutions
Possible Solutions

Recruit 4k computers and finish in a day

OR

Find a better method

better method
Better Method

Only specify the first symbol

Iterate through the results and only take results whose word following the joining symbol corresponds to a valid symbol

full query1
Full Query

“Jak2 acetylates OR phosphorylates OR methylates OR binds to OR interacts with”

another hindrance
Another Hindrance

The symbol “thE”

(and others like it)

Searches need to be case insensitive to account for “p53” and “P53”

Recognizes the word “the” as the protein “thE”

solution
Solution

Use a list of stop words

Very common, non-interesting words

If the name appears in that list of stop words, just forget about that protein all together

http://www.dcs.gla.ac.uk/idom/ir_resources/linguistic_utils/stop_words

methods cont
Methods (cont.)

After we have this data in a database...

Create a web interface to the data so others can search for protein interactions (Shwe)

slide16
Data

KEGG - Yeast MAPK

Our Data

http://www.genome.jp/dbget-bin/show_pathway?sce04010+YGR040W

data cont
Data (cont.)

KEGG - Yeast Cell Cycle

Our Data

http://www.genome.jp/dbget-bin/get_pathway?org_name=sce&mapno=04110

data cont1
Data (cont.)

Our Data

KEGG - Yeast 26S

Proteasome

http://www.genome.jp/dbget-bin/show_pathway?sce03050+YER012W

possible uses
Possible Uses
  • General reference for protein interactions
  • Curate other databases
final remarks
Final Remarks
  • Only works well detecting signal pathways and protein complexes
    • Not metabolic pathways
  • It is possible to get high quality, interesting data without much noise or complex text analysis algorithms
references
References

Kyoto Encyclopedia of Genes and Genomes http://www.genome.jp/kegg/

Cytoscape Network Visualization http://www.cytoscape.org/

Yahoo! Developer Network http://developer.yahoo.com/

acknowledgements
Acknowledgements
  • Dr. Matteo Pellegrini
    • Everyone in the lab
  • SoCalBSI
  • NIH / NSF