1. EBI is an Outstation of the European Molecular Biology Laboratory. Avazeh Ghanbarian Paul Kersey Alessandro Vullo EBI Microme Annotation Meeting June 2011

2. pkersey@ebi.ac.uk Microme Annotation Meeting June 201125.10.20152 Microme: current status We’re behind But we have some material: Curated data from the iAF1260 model (Anne’s presentation) Databases built on EcoCyc and MetaCyc Integration of different data sets A working reaction/pathway projection process Currently based on Ensembl Compara to identify orthologous proteins This is replaceable for future projections if a better system is proposed Generic rules for inferring complex/pathway completeness

3. pkersey@ebi.ac.uk Microme Annotation Meeting June 201125.10.20153 Microme: data decisions Integration work is not finished EBI has brought 3 databases to this meeting DB1: EcoCyc + MetaCyc DB2: EcoCyc + MetaCyc + curated iAF1260 data DB3: EcoCyc + projections Initial projection to ~30 species targetted for Biolog data We can use all 3 databases to assist the curation process Need to decide the basis for going forward – what is our reference database? Which database are we going to curate into?

4. pkersey@ebi.ac.uk Microme Annotation Meeting June 201125.10.20154 Microme: outputs Sets of inferred reactions for use in model building Semi-automated feedback loop for using model-building experience to improve reference data A UI to offer Microme reference and non-reference data to users

5. pkersey@ebi.ac.uk Microme Annotation Meeting June 201125.10.20155 Microme: web portal Before launch, EBI will prepare a lightweight portal giving access to all tools promoted by partners EBI will provide two components to this: A genome browser for the Microme reference species (using Ensembl technology) This will also provide access to the Compara-based orthology results An application for viewing pathways (using Reactome technology) We have been integrating the source data into a Reactome-style DB There is a curation tool for the direct addition of new pathways into this database

6. pkersey@ebi.ac.uk Microme Annotation Meeting June 201125.10.20156 The Reactome world view Reactome has a top down (i.e. pathway-centric) view of reactions in a species Data model and display can store reference pathways and projections Projections dynamically recalculated at intervals Reactome’s default is to project from one species to all others Microme will (in future) project from one generic reaction bin (containing all reference reactions) to all specific species Reactome’s data model is based on a recursive chain of “events”: in the data model, a reaction is simply an event in one or more pathways Curator UI reflects the data model User UI uses pathway as organising paradigm “is_a” and “part_of” relationships in Event hierarchy

7. pkersey@ebi.ac.uk Microme Annotation Meeting June 201125.10.20157 Microme interface: current status At this meeting, we only have interfaces based on the old version of the Reactome code The new code is much nicer and more powerful Interactive SBGN-based interface Allows upload of user expression data etc. Allows visualisation of projected pathways against the backdrop of the reference (shows what is present/absent against the backdrop of the full pathway). This requires us to draw pathway diagrams for our pathways This is a manageable task for the E. coli pathways 300 pathways, many can be drawn in a few minutes using the pathway curation tool

8. pkersey@ebi.ac.uk Microme Annotation Meeting June 201125.10.20158 Reactome UI

9. pkersey@ebi.ac.uk Microme Annotation Meeting June 201125.10.20159 Zoom Pathway dictionary This event Pathway diagram You are here

10. pkersey@ebi.ac.uk Microme Annotation Meeting June 201125.10.201510 Pathway diagrams can be complex (EcoCyc pathways less so) About this object

11. pkersey@ebi.ac.uk Microme Annotation Meeting June 201125.10.201511 External links Internal links

12. pkersey@ebi.ac.uk Microme Annotation Meeting June 201125.10.201512 External links Internal links Inferred entities in other species

13. pkersey@ebi.ac.uk Microme Annotation Meeting June 201125.10.201513 Reactome data may be of less use to us than Reactome software

14. pkersey@ebi.ac.uk Microme Annotation Meeting June 201125.10.201514 External links Internal links

15. pkersey@ebi.ac.uk Microme Annotation Meeting June 201125.10.201515

16. pkersey@ebi.ac.uk Microme Annotation Meeting June 201125.10.201516

17. pkersey@ebi.ac.uk Microme Annotation Meeting June 201125.10.201517 Analsysis tools

18. pkersey@ebi.ac.uk Microme Annotation Meeting June 201125.10.201518 User interface: conclusions This interface will work for us with the present data model But need to draw pathway diagrams first Mostly (much) simpler than Reactome pathways

19. pkersey@ebi.ac.uk Microme Annotation Meeting June 201125.10.201519 This workshop Understand how the curation tool works Curate some new reference pathways from literature Preliminary assessment of projection data Is it any good? How could it be improved to aid curation? How could it be used? Potential for writing analysis scripts to explore gaps, etc. How can we integrate this with Biolog data No formal time for this, but please talk to me if interested

20. pkersey@ebi.ac.uk Microme Annotation Meeting June 201125.10.201520 Microme: booting the data To use either version of the Reactome interface, we should organise data as pathways We have fitted the reactions curated by SIB and CEA into the EcoCyc framework of pathways If all the reactions in a pathway are not curated, using just some reactions might lead to the pathway becoming disconnected

21. pkersey@ebi.ac.uk Microme Annotation Meeting June 201125.10.201521 Microme: using MetaCyc We have also tried integrating MetaCyc Using only experimentally supported data Issues Many non-bacterial pathways Reference pathways and complexes may have exemplars from different species Don’t necessarily have a consistent set of exemplars to define a reference pathway Taxonomical resolution is various Some of the external curated Cyc databases not-usefully described in MetaCyc data file Too many pathways for us to draw

22. pkersey@ebi.ac.uk Microme Annotation Meeting June 201125.10.201522 MetaCyc: conlusions MetaCyc is fit for its own purpose, but it may make us ill trying to swallow it start with EcoCyc, and potentially progressively add additional sets of experimentally approved reactions from certain additional species

23. pkersey@ebi.ac.uk Microme Annotation Meeting June 201125.10.201523 Pathway comparison in current UI

24. pkersey@ebi.ac.uk Microme Annotation Meeting June 201125.10.201524 Pathway comparison in current UI

25. pkersey@ebi.ac.uk Microme Annotation Meeting June 201125.10.201525 Pathway comparison in current UI UniProt entry for the catalyst in this species