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Relations in GO for 2009

Relations in GO for 2009. Intro. We have many relations ready to GO live in the scratch directory within GO ontologies across GO ontologies between GO and external ontologies Both cross product (N+S conditions) and regular links

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Relations in GO for 2009

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  1. Relations in GO for 2009

  2. Intro • We have many relations ready to GO live in the scratch directory • within GO ontologies • across GO ontologies • between GO and external ontologies • Both cross product (N+S conditions) and regular links • Requires a fundamental change in how we and our users think about GO and annotations • Tools that make use of these will better serve users

  3. Relations in GO • In the beginning there was is_a and part_of • Benefits: simplicity • We could effectively ignore relations • Most tools and users effectively do this • Speculation: recent introduction of regulates had no effect on majority of users • Drawbacks: lack of expressivity • We need more relations • Regulation • Spatial relations • has_part for Process-Function • annotations

  4. Example of a relation rule in GO • Rule: • A is_a B, B is_a C  A is_a C • Example: • We can generalize this by having a rule for transitive relations • transitive r, A r B, B r C  A r C • We can also write this as a composition rule: • is_a . is_a is_a • Open question: • does this notation help or hinder??

  5. Transitivity • We currently have two transitive relations in GO: • is_a . is_a is_a • part_of . part_of part_of • Example: • mitotic prophase part_of mitosis • In GO, part_of is an all-some relation • regulates is not defined to be transitive in GO • (but the majority of tools still treat it as if it were!) • Example:

  6. Composition with is_a • Any relation that follows the all-some pattern composes with is_a to itself • Example: • (all) nucleus part_of (some) cell • Composition: • is_a . R R • R . is_a R • Example: • (all) mitotic prophase part_of (some) mitosis • mitosis is_a cell cycle phase •  • (all) mitotic prophase part_of (some) cell cycle phase

  7. Composition Table Read row first, the column (so far the table is symmetric)

  8. Composition Table • mitotic prophase part_of mitosis • is_a cell cycle phase •  • (all) mitotic prophase part_of (some) cell cycle phase

  9. Chained compositions • A part_f B is_a C is_a D part_of E •  • A part_of B is_a D part_of E •  • A part_of D part_of E •  • A part_of E order of reduction does not matter

  10. regulates transitive_overpart_of • regulates . part_of regulates inferred link inferred link

  11. regulates transitive_overpart_of • regulates . part_of regulates inferred link inferred link • (all) RoSPoMCC • regulates (some) MCC

  12. regulates transitive_overpart_of • regulates . part_of regulates inferred link inferred link • (all) RoSPoMCC • regulates (some) MCC

  13. Composition Table: Regulates

  14. Composition Table: Regulates regulates . part_of regulates

  15. Composition Table: Regulates part_of . regulates N/A

  16. regulates . regulates indirectly regulates We have the option of defining additional relations These may be entirely implicit (i.e. we would never assert indirectly regulates in GO)

  17. Regulates is not transitive Indirectly regulates is transitive

  18. USE SYMBOLS? OR IS THIS GETTING TOO ABSTRACT?

  19. Sub-relations • regulates • negatively_regulates • positively_regulates

  20. Sub-relations + indirect ~R R ~R+ ~R- R+ R- normal regulates relations asserted in GO indirect regulates relations never asserted, only implied

  21. Regulation relation lattice super-relation of indirect and direct regulation (call this one “regulates”?) ~RG ~RG+ ~RG- ~R RD ~R+ ~R- RD+ RD- renamed to DIRECTLY regulates? indirect regulates relations never asserted, only implied

  22. has_part • NOT the inverse of part_ofat the ontology level • Example: • nucleus part_of cell: YES • every nucleus is part_of some cell • by definition; e.g. extruded nuclei are ex-nuclei • cell has_part nucleus: NO • not every cell has_part nucleus • mammalian erythrocytes, bacteria • Example: • <pf example here> • <summarise pf progress>

  23. Annotations and relations • not just an ontology issue • this is of relevance to annotations too… • The current simple methodology of propagating annotations up the graph only works for a small subset of relations • To understand how annotations and new relations interact we must think in terms of gene product relations

  24. Gene product relations • What is the relation between a gene product and • A molecular function? • A biological process? • A cellular component? • Why care? • What’s wrong with “annotated_to”? • We need to define these relations: • to do justice to the biology • to be able to deal with new relations within the GO itself

  25. Why we should care • How should annotation queries, analysis tools (slimmers, enrichment tools) etc treat the (pseudo-)new regulates relation? • How should we recommend the process-function links be vizualized? • How should these links be treated in queries?

  26. Proposed relations for gene products • For MF and BP: • has_potential • has_function_during • For CC: • localized_to • This is more specific than has_location • A gene product may travel through different locations • Formally: • GP localized_to CC : GP executes some function in CC Names TBD MFs are ontologically like BPs (bfo processes)….

  27. How to read a GAF • <gene product> <rel> <GO term> • gene product may not be explicitly in GAF • that’s OK • gene as proxy • The relation does NOT apply to the gene however • genes are only localized_to chromosomes, and only participate in gene expression. It’s the products that do the work • <rel> is implicit, depending on F, C or P • Examples:

  28. Annotation relation composition • is_a • always propagate over is_a • localized_to . is_a  localized_to • has_function_in . is_a  has_function_in • part_of • localized_to . part_of localized_to • has_function_in . part_of  has_function_in • This is effectively what we do with gene product annotations now • post-hoc logical justification for why it’s OK to propagate

  29. Annotation relation composition: regulates • regulates • localized_to . regulates NEVER POSSIBLE • localized_to never has a process as target • regulates always has process as subject • has_function_in . regulates regulator_of • This introduces an addition implicit relation that can be used to sum gene product results • Fake AmiGO screenshot here

  30. Annotation relation composition: inter-ontology links • We have 183 CC->MF/BP links in scratch • regulates • localized_to . has_function_in ??may_contribute_to?? • Example: • RPS25A localized_to ribosome • ribosome has_function_in protein biosynthesis •  • RPS25A ??has_function_in?? protein biosynthesis • No need for curator to make explicit IC claims • Q: we never want “may” in relation names? • Can we make a stronger claim? • How does a curator know when to make an IC claim here? • Potential confusion with contributes_to qualifier

  31. Annotation relations and has_part • Need some graphical illustrations • See • http://wiki.geneontology.org/index.php/Has_part • for now

  32. Qualifiers • Annotation qualifiers (contributes_to) have the effect of modifying the relation • NOT is not a qualifier – it is a logical operator • We can add new relations to the qualifier column • geneProductA acted_on_during protein secretion by the type II secretion system

  33. Secondary taxon IDs

  34. Cell component relations • We have 674 xp defs within CC in scratch • adjacent_to • surrounds/surrounded_by • spans • overlaps • Use case: reactome • Can we say anything about gene products here? • we can perform spatial gene product queries

  35. Spatial reasoning • spans . adjacent_to  overlaps (??TBD!!) • SUN-KASH complex spans nuclear inner membrance • nuclear inner membrane adjacent_to nuclear lumen •  • SUN-KASH complex overlaps nuclear lumen

  36. Links from BP to external ontologies • Process-continuant links • A has_function_in cysteine biosynthesis •  A ??has_participant?? cysteine • this is true but can we make stronger claims • A has_function_in heart development •  A has_participant heart • c.f. heart process, TAZ gene • How can we use this? • Browse GO annotations via other ontologies • Enrichment using anatomy terms… • AmiGO screenshots

  37. what next?

  38. Won’t this confuse users? • We will provide a pre-made inferred relation table for all of GO • we could do this for gps too but it would be over a billion entries.. • We can always distribute a dumbGO • just is_a and part_of, not even regulates • Need more guidance on how this can be used

  39. Discussion

  40. What’s next? • Move relations into GO editors file • post OE2 • CC-self • spatial relations • BP->MF • has_part • regulates • BP->BP • has_part (??) • External onts • Dual releases? dumbGO and fullGO? • Fix GOC tools (AmiGO, slimmer, enrichment, graphviz, refG) to deal appropriately • OE2 should already be fine • Educate non-GOC folks

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