A database of biological pathways and processes

(borrowed from a presentationcreated by Steve Jupe)

http://biocyc.org/ARA/new-image?type=PATHWAY&object=PWY-695

http://biocyc.org/ARA/NEW-IMAGE?type=REACTION-IN-PATHWAY&object=RXN-698

What about these?-protein-protein and protein-small molecule interactions (noncovalent and covalent)- effects of location within cell- and …

Cutler et al. (2010) “Abscisic acid: emergence of a core signaling network” Annu Rev Plant Biol 61:651–79

Nambara & Marion-Poll (2005) “Abscisic acid biosynthesis & catabolism” Annu Rev Plant Biol 56:165-85

Seo & Koshiba (2002) “Complex regulation of ABA biosynthesis in

plants” Trends Plant Sci 7:41-8

… and integration of signaling and regulation with metabolism

Seo & Koshiba (2002) “Complex regulation of ABA biosynthesis in plants” Trends Plant Sci 7:41-8

Some of the regulatory links that can potentially be annotated

Reactome is- reductionist. All of biology can be represented as events that convert input physical entities into output physical entities.- a generic parts list. Tissue and state specificity of events are not captured.- qualitative. Kinetic parameters and data are not captured.- species-centric. Experiments may use reagents from diverse sources, but most biological processes take place in single species, and the focus here will be on rice biological processes.- manually curated. Events are annotated by expert curators, and linked to published data.- open source. All data and software are freely downloadable and reusable.

Data model in a nutshell

Pathway

Pathway Reaction Reaction

CatalystActivity

Output 1

Reaction

Input 1

Input 2 Output 2

Regulation

A geometrical compartment set for locating molecules in human cells

Incomplete! What needs to be added or changed to locate molecules in plant cells?

Why ‘Reactome’?• Reactions are the ‘units’ of a pathway (network)

• Capture events and changes of state found in biology

TRANSPORTCLASSIC

BIOCHEMICAL

BINDING

DISSOCIATION

DEGRADATION

PHOSPHORYLATION

DEPHOSPHORYLATION

Reactome Aims• Represent detailed biological pathways

composed of ‘biological events’• Describe every step (interaction or other

event)• Provide evidence from literature for every

step• Make available free for browsing and

download/re-use• Store in a computationally accessible way

(support multiple download standards/formats)

• Link to external resources and use standard IDs, nomenclature wherever possible

rice

PMID:5555 PMID:6666

Arabidopsis

tobacco

Direct evidence

Indirect evidence(inference)

PMID:7777

PMID:8888

Using model organism data to build pathways – inferred reactions

LOC:1111 LOC:1112 LOC:1113 LOC:1114

UniProt:P11111

UniProt:P22222

How do we accommodate rice subspecies (strains)?How do we link between fully curated databases (Arabidopsis and rice)?

Reaction Example 1: Enzymatic

Reaction Example 2: Transport

REACT_1338.3

Other Reaction Types

DimerizationPhosphorylation

Reactions Connect into Pathways

OUTPUTINPUT

CATALYST

OUTPUTINPUT

CATALYST

INPUT OUTPUT

CATALYS

T

Data Expansion - Link-outs From Reactome

• GO – Molecular Function– Compartment– Biological process

• ChEBI – small molecules• UniProt – proteins• PubMed references – literature evidence for

events• Sequence dbs – Ensembl, OMIM, Entrez

Gene, RefSeq, HapMap, UCSC, KEGG Gene