A database of biological pathways and processes (borrowed from a presentation created by Steve Jupe)

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: 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 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 TRANSPORT CLASSIC 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:1111LOC:1112LOC:1113LOC: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 Dimerization Phosphorylation

Reactions Connect into Pathways OUTPUT INPUT CATALYST OUTPUT INPUT CATALYST INPUT OUTPUT CATALYST

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