1. Networks and Pathways I
First & Last Name
February X, 2003
Networks and Pathways I
CBW Bioinformatics Workshop
February 24th 2005, Vancouver
Christopher Hogue
The Blueprint Initiative
Lecture 10.3
(c) 2003 CGDN

2. About this talk The Problem of Choice – Too Many Databases
First & Last Name
February X, 2003
About this talk
The Problem of Choice – Too Many Databases
Data Exchange Formats
Pathway Resources
KEGG
EcoCyc
Small Molecule Resources
PubChem
SMID-BLAST
Lecture 10.3
(c) 2003 CGDN

3. Molecular Assembly Data
Interaction pair
“A binds B”
Database of Interactions
Molecule = Vertex
Interaction = Edge
Tools/Computations
Graph Theory
Pathway Finding
Simulations
Cellular CAD
Goodsell

4. Molecular Assembly What Databases to use?
First & Last Name
February X, 2003
Molecular Assembly What Databases to use?
DNA
RNA
Proteins
Small molecules
Complexes
Lecture 10.3
(c) 2003 CGDN

5. First & Last Name
The Problem
February X, 2003
So many assembly databases, all with their own data models, formats, and data access methods.
Include the number 138 in larger font
Lecture 10.3
(c) 2003 CGDN

6. User Behavior The problem of too much choice.
(M. and S.
Two tables in a supermarket:
24 jars of jam vs 6 jars of jam.
3% vs 30%
Choice frustration.
Leads to incrementalism – as essential user criticism is withdrawn.
Can’t Debug - This jam is a little bitter compared to
the other 6?
the other 26?
A whole lot of bad jam that nobody wants to buy…
Lecture 10.3

7. User Behavior The problem of too much choice.
(M. and S.
Two tables in a supermarket:
24 jars of jam vs 6 jars of jam.
3% vs 30%
Choice frustration.
Leads to incrementalism
Essential user criticism is withdrawn.
Can’t Debug - This jam is a little bitter compared to
the other 6?
the other 24?
A whole lot of bad jam that nobody wants to buy…
Lecture 10.3

8. Standards Fatigue
Data Standards are not an effective goal to achieve results in a timely way
Interactions/Pathways since NIH meeting in Nov Efforts are still not integrated (PSI/IMEX and BIOPAX).
Information Systems are better goals.
Wet Lab Scientists are busy people who are (excuse me) trying to write papers.
Ongoing wishful thinking about latest new technology.
If only we had the semantic web – it wouldl fix everything!
Lecture 10.3

9. “Community” Standards
IMEX (BIND/DIP/INTACT/MINT/MIPS)
BioPAX (pathway databases)
SBML (>70 software systems collaborating)
Cytoscape (collaborating interface developers)
NCBI/Blueprint (architecture)
Model Organism Databases (GMOD architecture)
Journals and Editors
Scientific Societies (FASEB)
Member and Non-member Scientists
Lecture 10.3

10. Interaction Standards - PSI
Lecture 10.3

11. BioPAX – Pathways/Reactions
Lecture 10.3

12. Exchange Formats in the Pathway Data Space
First & Last Name
February X, 2003
Database Exchange
Formats
Simulation Model
Exchange Formats
BioPAX
Genetic
Interactions
SBML,
CellML
PSI-MI 2
Regulatory Pathways
Low Detail High Detail
Interaction Networks
Molecular Non-molecular
Pro:Pro TF:Gene Genetic
Rate
Formulas
Molecular Interactions
Pro:Pro All:All
Biochemical
Reactions
This slide shows the difference between exchange formats in the pathway data space. Pathway databases and tools are not considered here, although each one is important and addresses specific use cases. I would use the other slide which shows the scope of BioPAX level 1. You can always point out that BioPAX intends to cover the whole space. It is important not to overstate the current state of things.
BioPAX level 1 is broad and shallow allowing us to quickly build a format that can represent most the existing data types in databases today. Details will be added in subsequent levels. This is a practical approach.
Metabolic Pathways
Low Detail High Detail
Small Molecules
Low Detail High Detail
Lecture 10.3
(c) 2003 CGDN

13. Two Views on Biomolecular Assembly Data Integration
Separate Models
Pathways
Interactions
Separate Databases
Multiple DB ontologies
Ad-hoc curation standards
Ontology Consortia
PSI
BioPAX
APIs – Exchange Only
Publish or perish
Unified Model
Networks with Interactions and Reactions
GenBank-Like Data Archive
One Ontology archiving all
Professional Curation
Single Curation Standard
FTP Services
APIs – Atomistic Objects
Service or perish
Lecture 10.3

14. Where to define data objects? API or Exchange or Archive?
Software Systems Components (OSI Layers…)
Human Interfaces
Application Programming Interfaces
Communications Protocols (Exchange)
Content Structure (Archive)
Database (ODBC/JDBC compliant MySQL)
Document Structures (XML)
Architectures (Compatible orchestration of the above)
Platforms (Runs the above: Windows, Linux, Unix)
Atomistic
All-or-none
Lecture 10.3

15. BioPAX Motivation
First & Last Name
February X, 2003
Common format will make data more accessible, promoting data sharing and distributed curation efforts
Application
Data loss…
Database
Designed by the databases for themselves (DB-DB exchange) and for users. Umm… not really for users, yet. Unless you integrate into SBML
User
With BioPAX
Before BioPAX
>150 DBs and tools
Lecture 10.3
(c) 2003 CGDN

16. Pathways, Interactions and Signaling
First & Last Name
February X, 2003
Pathways, Interactions and Signaling
Also include gene regulation
Metabolic
Pathways
Molecular
Interaction
Networks
Signaling
Pathways
Lecture 10.3
(c) 2003 CGDN

17. Lecture 10.3

18. Summary: Working with a spectrum of communities.
Identify the communities.
Recognize that communities are disjoint.
Success will arise from broad collaboration across the spectrum of identified communities.
Service all communities effectively with a whole system.
Drive innovation more through applications development and use.
Gain and effectively incorporate user critique.
Understand user needs, behaviors.
Lecture 10.3

19. Pathway Databases
KEGG and EcoCyc
Lecture 10.3

20.
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34. PubChem – Small Molecules
Lecture 10.3

35. PubChem Substance Compound
descriptions of chemical samples, from a variety of sources, and links to PubMed citations, protein 3D structures, and biological screening results that are available in PubChem BioAssay.
If the contents of a chemical sample are known, the description includes links to PubChem compound.
Compound
Includes mixtures
Lecture 10.3

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39. Similarity Search Similar Compounds Links – PubChem Bioassay
Lecture 10.3

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45. Small Molecule Interaction DB.
SMID-BLAST - for finding small molecule binding sites based on 3D structures.
Lecture 10.3

46. Lecture 10.3

47. What’s in SMID? SMID-BLAST?
SMID is a derived relational database
3D structures that have small molecule binding sites
CDD domain regions – families of conserved domains
Small molecule binding residues are mapped onto CDDs.
SMID-BLAST enhances domain searching with small molecule binding context.
Lecture 10.3

48. Proteomics – HUPO Poster
Proteomics – Phenol upregulated protein in H. salinarium.
Spots identified by 2D gels of +/- 1mM Phenol in 4.5M NaCL
Han, Han, Kim, Joo and Chan-Wha Kim, Korea University
H. salinarium is not sequenced –
Mass spec peptide hits to Halobacterium sp. NRC-1
GI (Vng2406c) and
GI (Vng2339c)
Poster authors presented no conclusions other than that these were completely unknown proteins.
Lecture 10.3

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50. Little information from CDD…
Lecture 10.3

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53. Completely relaxed
Search settings…
Lecture 10.3

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55. Aromatic ligand binding site – phenol…
Lecture 10.3

56. Oxygen
Reactive
site
Lecture 10.3

57. SMID-BLAST
Offers small molecule context in addition to CDD domain hits
With SMID-BLAST we can speculate on how two proteins work to utilize Phenol as a carbon source
Reactive species and “loose” specificity hydrophobic binding sites.
Lecture 10.3

58. SMID-BLAST Standalone
Scoring System
Distinguishes site specificity
Weights substrate/binding site size
Generates GenPept Annotation
Suitable for use in sequence analysis pipelines
Lecture 10.3