# Presentation: 196864

## NCICB Pathway Interaction Database

- 19 February 2004

## Problem

- Most collections of pathway data are not computable
- can’t merge pre-defined pathways
- can’t find 1st-degree, 2nd-degree downstream interactions, ...
- can’t propagate hypothesized effect of anomalies
- can’t mix data sources (high-throughput & curated data)
- Prototype Pathway Interaction Database
- http://cmap.nci.nih.gov/PW
- See if sufficient data is available
- Experiment with representations
- See what users want
- Try out algorithms

## Goals

- Merge data from multiple sources
- Construct cause/effect networks dynamically
- Offer rich set of query options
- molecule, interaction, pathway, successor/precedessor, prune, connect, ...
- Associate values (e.g. expression level) with molecules & propagate across the network
- Offer text and graphic output
- Scale to large network
- currently, graphic output is limiting factor

## NOT Among Current Goals

- Custom pathway layouts or artistic renderings
- Encyclopedic or unstructured knowledge about interactions
- Representing multi-cellular processes
- Controlled vocabulary for pathway names

## Representation (1 of 2)

- Pathway: directed graph
- node: molecule or event or condition
- edge: role of molecule/condition in an event
- interaction: event &  its connected molecules/conditions
- Molecule type:
- protein | complex | compound | rna
- or families (e.g. EC_2.7.7.15 includes PCYT1A, PCYT1B)
- Event type:
- reaction | modification | transcription | translocation
- or any GO BP type

## Representation (2 of 2)

- Condition type:
- any GO BP type
- Role type:
- input | output | agent | inhibitor
- or any GO MF type
- Molecule location
- any GO CC type
- specified at point of use
- Posttranslational modification
- abstract terms (e.g. “active”)
- specified at point of use

## Accessing Data

- http://cmap.nci.nih.gov/PW
- HTML forms
- Command language
- file upload
- post to web service
- Rudimentary data input tool

## Query Options

- Basic query
- by set of molecules
- by set of predefined pathways
- Query modifiers
- upstream/downstream interactions
- connect molecules (arbitrary shortest connection)
- prune molecules
- collapse distinctions among posttranslational mods
- collapse graph by removing process nodes

## Output Options

- HTML
- individual molecule & interaction pages
- Text
- native XML
- SBML
- Graphic
- GIF
- SVG

## Example: ATM and Successors

**Example: ATM and Successors**

## Current Contents (all human)

- Interaction Types

## Technical Details

- Oracle (~25 tables)
- no Oracle-specific features used
- Perl (~10K lines)
- query parsing
- retrieval from DB
- graph operations & value propagation
- output
- a bit of Python; HTML
- For layout, “dot” tool (open source, part of GraphViz)
- http://www.research.att.com/sw/tools/graphviz/

## Related Projects

- pathway interaction data
- BIND
- http://www.blueprint.org/bind
- Genome Knowledge Base
- http://www.genomeknowledge.org
- pathway construction/analysis tools
- Cytoscape
- http://www.cytoscape.org

## Possible Future Steps

- Create caBIO objects for Pathway Interaction Database [4 mos.]
- Standardize on XML representation [1 mo.]
- BioPAX likely to be more appropriate than SBML
- Implement standard (e.g. SOAP) web services interface [1 mo.]
- Remove Zope/Python dependencies and package for installation [2 mos.]
- Further data acquisition [open-ended]