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A Database of human biological pathways Bijay Jassal

A Database of human biological pathways Bijay Jassal. Outline. What is Reactome? Theory Basic data-model Expansion Release cycle Curator Tool Example – curation Example – diagram drawing. Reactome is…. Free, online, open-source curated

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A Database of human biological pathways Bijay Jassal

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  1. A Database of human biological pathways BijayJassal

  2. Outline • What is Reactome? • Theory • Basic data-model • Expansion • Release cycle • Curator Tool • Example – curation • Example – diagram drawing

  3. Reactome is… Free, online, open-source curated database of pathways and reactions in human biology Authored by expert biologists, maintained by Reactome editorial staff (curators) Mapped to cellular compartment

  4. Reactome is… Extensively cross-referenced Tools for data analysis – Pathway Analysis, Expression Overlay, Species Comparison, Biomart… Used to infer orthologous events in 20 non-human species

  5. BINDING DEGRADATION DISSOCIATION DEPHOSPHORYLATION PHOSPHORYLATION CLASSIC BIOCHEMICAL TRANSPORT Theory - Reactions Pathway steps = the “units” of Reactome = events in biology

  6. Reaction Types Dimerization Binding Transport Phosphorylation Biochemical

  7. Reactions – physical location of entities plasma membrane

  8. Reactions Connect into Pathways CATALYST CATALYST CATALYST INPUT OUTPUT INPUT OUTPUT OUTPUT INPUT

  9. Basic Reactome data model PhysicalEntity (SimpleEntity)) Glucose (cytosol) CHEBI:17925 Glucose (extracellular) ReferenceEntity PhysicalEntity (EWAS) AKT1 (nucleoplasm) compartment AKT1 (cytosol) UniProt:P31749 Phosphorylated AKT1 (cytosol) Altered state PDK1:AKT1 (cytosol) complexed

  10. Basic Reactome data model Event (Pathway) CatalystActivity PubMed (lit reference) BiologicalProcess (GO) PhysicalEntity (ReferenceEntity) MolecularFunction (GO) Compartment (GO) Catalyst PhysicalEntity (ReferenceEntity) PhysicalEntity (ReferenceEntity) Compartment (GO) Compartment (GO) Input(s) Output(s) Event (Reaction) PubMed (lit reference) Compartment (GO)

  11. Frequently used classes Event Pathway Reaction PhysicalEntity Protein (EWAS) Complex Sets CatalystActivity LiteratureReference Compartment Species Summation

  12. Link-outs from Reactome Compartment, MolecularFunction BioGPS UniProt ChEBI CTD KEGG Compound dbSNP Ensembl UCSC PubChem Entrez Gene

  13. Evidence Tracking – Inferred Reactions Direct evidence PMID:5555 PMID:4444 Human pathway Indirect evidence PMID:8976 mouse PMID:1234 cow

  14. Data Expansion – Projecting to Other Species Human B A A + ATP -P + ADP Mouse B A A + ATP + ADP -P Drosophila Reaction not inferred B + ATP A No orthologue - Protein not inferred

  15. FIX DATA REVIEW DATA Release overview Expert data Curator Curator Tool Central DB Data Expansion - electronic inference links added Stable Ids added Release DB

  16. Diagram example

  17. Reactome’s Curator Tool (CT)

  18. Download instructions

  19. Curator Tool – schema view

  20. CT - hierarchical view

  21. CT – ELV view

  22. Curation example Biosynthesis of UDP-N-acetyl-L-fucosamine, a Precursor to the Biosynthesis of Lipopolysaccharide in Pseudomonas aeruginosa Serotype O11* (PubMed:15778500)

  23. Pathway: UDP-L-FucNAc biosynthesis http://wiki.reactome.org/index.php/New_Reactome_Curator_Guide Create instance of Pathway class with name, summary and literature reference(s) Reactions • C4, C6 dehydratation of UDP-D-GlcNAc • C5 Epimerization with UDP-D-GlcNAc • C3 epimerization of UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-hex-4-ulose(2-) • C4 reduction of UDP-2-acetamido-2,6-dideoxy-beta-L-xylo-4-hexulose(2-) • Epimerization of UDP-L-PneNAc

  24. Reaction 1: C4, C6 dehydratation of UDP-D-GlcNAc Pseudomonas aeruginosa UniProt:Q9XC61 GO MF:0016836 CHEBI:57705 NEW CHEBI:62375 UDP-2-acetamido-2,6-dideoxy-alpha;-D-xylo-4-hexulose (2-)

  25. Reaction 2: C5 Epimerization with UDP-D-GlcNAc Pseudomonas aeruginosa UniProt:Q9XC61 GO MF:0016857 NEW CHEBI:62375 NEW CHEBI:60101 UDP-2-acetamido-2,6-dideoxy-alpha;-D-xylo-4-hexulose (2-) UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-hex-4-ulose(2-)

  26. Reaction 3: C3 epimerization of UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-hex-4-ulose(2-) NEW CHEBI:60101 UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-hex-4-ulose(2-) Pseudomonas aeruginosa UniProt:Q9XC60 GO MF:0016857 NEW CHEBI:62377 UDP-2-acetamido-2,6-dideoxy-beta-L-xylo-4-hexulose(2-)

  27. Reaction 4: C4 reduction of UDP-2-acetamido-2,6-dideoxy-beta-L-xylo-4-hexulose(2-) NEW CHEBI:62377 NEW CHEBI:62372 UDP-2-acetamido-2,6-dideoxy-beta-L-xylo-4-hexulose(2-) Pseudomonas aeruginosa UniProt:Q9XC60 GO MF??

  28. Reaction 5: Epimerization of UDP-L-PneNAc NEW CHEBI:62372 UDP-L-FucNAc (CHEBI:62241) Possible modification stereoisomery of C1 of CHEBI:62241 (racemic) to alpha stereoisomer Pseudomonas aeruginosa UniProt:Q9XC59 GO MF:0016857

  29. Draw the pathway diagram (ELV)

  30. OICR Lincoln Stein (PI) Bruce May, Guanming Wu, Robin Haw, Marija Orlic-Milacic, Karen Rothfels, Joel Weiser, Christina Yung, Cheryl Song EBI Ewan Birney (co-PI), Henning Hermjakob (co-PI) David Croft, Bijay Jassal, Phani Vijay Garapati, Steven Jupe, Mark William, Antonio Fabregat Mundo NYU Peter D’Eustachio (co-PI; editor-in-chief) Lisa Matthews, Marc Gillespie, Mike Caudy, Veronica Shamovsky • NHGRI P41 HG003751 • EU Sixth Framework Programme (LSHG-CT-2003-503269) • EBI Industry program Grants The Team e-mail: help@reactome.org

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