1. 1 SRI International Bioinformatics BioCyc Tutorial Peter D. Karp, Ph.D. Bioinformatics Research Group SRI International pkarp@ai.sri.com BioCyc.org EcoCyc.org, MetaCyc.org, HumanCyc.org http://www.ai.sri.com/pkarp/talks/biocyc- tutorial.ppt

2. 2 SRI International Bioinformatics A Roadmap to BioCyc BioCyc Content BioCyc Web site l Object pages l Genome browser l Overviews and omics viewers l Comparative analyses Desktop BioCyc How to learn more

3. 3 SRI International Bioinformatics What is BioCyc? A rich information source that connects genomes and metabolic pathways Couples curated data with computational predictions Supports analysis of omics data Provides comparative analysis tools Microbial emphasis. Exceptions: l Human PGDB l Non-SRI PGDBs outside BioCyc

4. 4 SRI International Bioinformatics BioCyc Content

5. 5 SRI International Bioinformatics BioCyc Collection of Pathway/Genome Databases Pathway/Genome Database (PGDB) – combines information about l Pathways, reactions, substrates l Enzymes, transporters l Genes, replicons l Transcription factors/sites, promoters, operons Tier 1: Literature-Derived PGDBs l MetaCyc: Experimentally elucidated metabolic pathways and enzymes l EcoCyc: Model organism database for Escherichia coli K-12 Tier 2: Computationally-derived DBs, Some Curation -- 20 PGDBs l From SRI: HumanCyc, Mycobacterium tuberculosis l From other groups: Tier 3: Computationally-derived DBs, No Curation -- 349 PGDBs

6. 6 SRI International Bioinformatics BioCyc Tiers Tiers 1-2 l Experimental data, curated from the literature l Rich, extensive, accurate l Contain types of data that can’t be predicted computationally Tier 3 DBs created by subjecting annotated genomes to PathoLogic computational processing pipeline: l Pathway prediction l Pathway Hole Filling l Operon prediction (bacteria) l Transport Inference Parser 349 PGDBs l Source: CMR database Tier 3 will be regenerated and expanded on a regular basis

7. 7 SRI International Bioinformatics Hundreds of Other PGDBs Available Outside BioCyc In all domains of life Tiers 2-3 See BioCyc.org for exhaustive list Their Web sites also powered by Pathway Tools Examples include l Yeast, Candida albicans, Dictyostelium l Mouse l Arabidopsis, Solanaceae, Medicago, Gramene

8. 8 SRI International Bioinformatics Curate Your Own PGDB We encourage other groups to establish curation efforts Adopt a BioCyc PGDB Build your own PGDB with Pathway Tools Pathway Tools is the software used to create, update, query, and visualize BioCyc DBs Contact: biocyc-support@ai.sri.com

9. 9 SRI International Bioinformatics Pathway/Genome Database Chromosomes Plasmids Genes Proteins RNAs Reactions Pathways Compounds CELL Operons Promoters DNA Binding Sites Regulatory Interactions Sequence Features

10. 10 SRI International Bioinformatics BioCyc Web Site

11. 11 SRI International Bioinformatics BioCyc Object Pages Genes Genome browser Transcription units Proteins l Enzymes, transporters, transcription factors, others l Extensive comments and citations l Monomers and multimers are represented, and in different chemical states RNAs Reactions Pathways Compounds Searches are organized around the object types!

12. 12 SRI International Bioinformatics BioCyc Searches Basic search l http://biocyc.org/server.html http://biocyc.org/server.html

13. 13 SRI International Bioinformatics BioCyc Searches Advanced search l http://biocyc.org/query.html http://biocyc.org/query.html

14. 14 SRI International Bioinformatics Genome Browser

15. 15 SRI International Bioinformatics Comparative Analysis

16. 16 SRI International Bioinformatics Pathway Tools Overviews and Omics Viewers Diagrams designed to avoid the hairball effect Generated automatically from PGDB Zoom, interrogate Omics viewers paint omics data onto overview diagrams l Provide different perspectives on the same dataset l Animation can be used for multiple time points or conditions l Can paint any data that associates numbers with genes, proteins, reactions, or metabolites Overviews provide genome-scale visualizations of cellular networks Harness the power of the human visual system to interpret patterns in biological contexts

17. 17 SRI International Bioinformatics Desktop BioCyc

18. 18 SRI International Bioinformatics Desktop BioCyc Linux/PC, Windows/PC, Macintosh (in March) Why install locally? Runs faster Significantly more functionality l More searches l Regulatory Overview, Genome Overview, Metabolite Tracing Write programs using APIs Access BioCyc when you can’t access the Internet See: http://biocyc.org/download.shtmlhttp://biocyc.org/download.shtml

19. 19 SRI International Bioinformatics Metabolite Tracing

20. 20 SRI International Bioinformatics Comparison of BioCyc to KEGG KEGG approach: Static collection of pathway diagrams that are color-coded to produce organism-specific views KEGG vs MetaCyc: Resource on literature-derived pathways l KEGG pathways maps are composites of pathways in many organisms -- do not identify what specific pathways elucidated in what organisms l KEGG has no literature citations, no comments, less enzyme detail KEGG vs BioCyc organism-specific PGDBs l KEGG re-annotates entire genome for each organism l KEGG does not curate or customize pathway networks for each organism Software tools l KEGG has no algorithmic visualization tools l KEGG has no queryable metabolic-map overview diagram l KEGG has no interactive editing tools

21. 21 SRI International Bioinformatics BioCyc and Pathway Tools Availability WWW BioCyc freely available to all l BioCyc.org BioCyc DBs freely available to non-profits l Flatfile downloads in multiple formats from BioCyc.org Pathway Tools freely available to non-profits l PC/Windows, PC/Linux, SUN

22. 22 SRI International Bioinformatics How to Learn More

23. 23 SRI International Bioinformatics Learn More BioCyc Web Seminars (Webinars) l http://biocyc.org/webinars.shtml http://biocyc.org/webinars.shtml BioCyc Publications l http://biocyc.org/publications.shtml http://biocyc.org/publications.shtml

24. 24 SRI International Bioinformatics Acknowledgements SRI l Suzanne Paley, Ron Caspi, Ingrid Keseler, Carol Fulcher, Markus Krummenacker, Alex Shearer EcoCyc Collaborators l Julio Collado-Vides, Robert Gunsalus, Ian Paulsen MetaCyc Collaborators l Sue Rhee, Peifen Zhang, Kate Dreher l Lukas Mueller, Anuradha Pujar Funding sources: l NIH National Center for Research Resources l NIH National Institute of General Medical Sciences l NIH National Human Genome Research Institute BioCyc.org Learn more from BioCyc webinars: biocyc.org/webinar.shtml