+ Multi-organism GO annotation David Osumi-Sutherland Gene Ontology

+

+ “rif... [is] expressed on the infected red [blood] cell surface.” Plasmodium falciparum GP of one organism in CC of another

+ Plasmodium falciparum | Homo sapiens The species in the interaction are recorded... by entering two taxon IDs in the Taxon column: First taxon ID: species encoding the gene product First taxon ID: other species in the interaction. GP of one organism in CC of another

+ Plasmodium falciparum | Homo sapiens The species in the interaction are recorded... by entering two taxon IDs in the Taxon column: First taxon ID: species encoding the gene product First taxon ID: other species in the interaction. Why not just plasma membrane? GP of one organism in CC of another

+ A duplicate cell component branch is growing under host-cell Why? Keeps annotations of gene products located in CCs of host organism separate from regular GO CC annotations.

+ A duplicate cell component branch is growing under host-cell Many terms duplicate the regular cell component hierarchy. THIS IS NOT SUSTAINABLE Some terms refer to components that are formed from the interaction of 2 organisms. Add new parent class for these: multi-organism cell component

+ Proposed solution Plasmodium falciparum parasite_of Homo sapiens located_in GO: plasma membrane + annotation extension: part_of Homo sapiens

+ Proposed solution Plasmodium falciparum parasite_of Homo sapiens located_in GO: plasma membrane When used, replaces part_of as default GP to CC relation in GPAD Tools used for grouping annotations need to group these annotations separately. Precedent: NOT New qualifier / GP to CC relation: located_in + annotation extension: part_of Homo sapiens

+ Proposed solution Plasmodium falciparum parasite_of Homo sapiens located_in GO: plasma membrane New qualifier / GP to CC relation: located_in + annotation extension: part_of Homo sapiens Replace host CC term with regular one, recording the taxon of the organism it is part of in the annotation extension.

+ Proposed solution Plasmodium falciparum parasite_of Homo sapiens located_in GO: plasma membrane Taxon extension – using standard relations between organisms : host_of, symbiont_of, parasite_of vector_for… Relations defined with population and community ontology (PCO) + annotation extension: part_of Homo sapiens

+ Proposed solution – retrofit when host not recorded Plasmodium falciparum symbiont_of host organism * located_in GO: plasma membrane + annotation extension: part_of host organism * * Generic host organism class from PCO

+ Homo sapiens | Human rhinovirus 3 Multi-organism process annotation

+ Homo sapiens host_of Human rhinovirus 3 Proposed solution + annotation extension: occurs_in Homo sapiens Optionally record where the process takes place

+ mate_of host_of, parasite_of, vector_for host_of/parasite_of bitten_by ? pregnant_mother_of ? / fetus_of ?

+ What does annotation mean? Too strong: All instances of the RIF gene product are located in some plasma membrane that is part of some Homo sapiens. All instances of the ICAM-1 gene product are involved in some HRV3 virion attachment to (human) host cell.

+ Capabilities are not necessarily realised All sperm capable_of (some) fertilization But not all sperm do. In fact most do not. All ICAM-1 gene product capable_of_part_of some ‘virion attachment to host cell’ But most don’t.

+ LEGO-ish class level formalisation of ‘lego’ brick Gask3 SubClassOf: capable_of some ('protein kinase activity' that (part_of some 'canonical wnt signalling’) and (occurs_in some cytosol)) protein kinase activity canonical Wnt signaling P Gask3 b cytosol

+ The same pattern works for three separate annotations Gask3 SubClassof: capable_of some 'protein kinase activity’ capable_of some('molecular_function' that (part_of some 'canonical wnt signalling')) capable_of some ('molecular_function' that (occurs_in some cytosol)) protein kinase activity canonical Wnt signaling P Gask3 b cytosol

+ Using this pattern for localisation to CC of an interacting organism RIF subClassOf: capable_of some ( 'molecular function' that occurs_in_location some ( 'plasma membrane' that part_of some ( 'Homo sapiens' that host_of some 'Plasmodium falciparum 3D7’ ) occurs_in_location = more general version of occurs_in that entails location rather than parthod

+ Using this pattern for multi- organism process ICAM1 subClassOf: capable_of some ( 'molecular function' that part_of some ( 'receptor-mediated virion attachment to host cell' that occurs_in some ( ‘Homo sapiens' that host_of some 'Human rhinovirus 3' ) ICAM1 encoded_by some Homo sapiens

+ Ba71V-98 subClassOf: capable_of some ( 'molecular function' that part_of some ( 'virion attachment to host cell' that occurs_in some ( Cercopithecus aethiops that host_of some 'African swine fever virus’ ) Ba71V-98 encoded_by some ‘African swine fever virus’ ASFV virion Using this pattern for multi- organism process

+ Multi-organism lego brick ICAM1 subClassOf: capable_of some ( ’protein binding' that part_of some ( 'receptor-mediated virion attachment to host cell' that occurs_in some ( ‘plasma membrane’ that part_of some ( ‘Homo sapiens' that host_of some 'Human rhinovirus 3’ ) ICAM1 encoded_by some Homo sapiens

+ OWL DEMO

+ But this pattern can’t work directly for Lego construction Visualization protein kinase activity canonical Wnt signaling P Gask3 b cytosol protein binding Btrc cytosol required_for Individual: gobp Types: ‘cannonical wnt signaling’# Individual: gomf Types: ‘protein kinase activity occurs_in some cytosol, enabled_by some PR:P87654 Facts: required_for gomf Individual: gomf Types: ‘protein binding’, occurs_in some cytosol, enabled_by some Btrc

+ Pattern is incompatible with current Lego pattern Visualization protein kinase activity canonical Wnt signaling P Gask3 b cytosol protein binding Btrc cytosol required_for Individual: gobp Types: ‘cannonical wnt signaling’# Individual: gomf Types: ‘protein kinase activity occurs_in some cytosol, enabled_by some PR:P87654 Facts: required_for gomf Individual: gomf Types: protein binding, occurs_in some cytosol, enabled_by some Btrc Note – CC & GP are classes

+ Possible Solutions: Parallel translations? Same basic pattern used in each case Lego bricks capture a set of related findings in a single paper Class level assertion makes sense for this Lego construction captures a model of how these fit together under some circumstances… Change LEGO pattern CC & GP both become individuals

+ Acknowledgments Jane Lomax Rebecca Foulger Chris Mungall Ramona Walls (PCO – relation defs) Jie Zheng (PCO – relation defs)