Refining Gene Ontology to Include Terms and Relationships Relevant to exRNA Communications

1
An ontology is used to represent domain knowledge in a standard machine-readable way to enable data annotation, discovery, and integration. The Extracellular RNA Communication Consortium has established an ontology group to work towards standardization and classification of the terms used to describe extracellular vesicles (EVs). As part of this ontology effort, we have worked with domain experts and ontology experts to propose new terms and relationships that can be added to the widely-used Gene Ontology (GO) for describing EVs and other exRNA-containing particles. Our proposal reflects broad community consensus, as it was reviewed and approved by: International Society for Extracellular Vesicles American Society for Exosomes and Microvesicles. In this attempt to standardize exRNA-related terminology, we strive to strike a balance between the lumperand “splitter” approaches in this new and incompletely understood domain. We are currently working closely with the GO Consortium to incorporate the proposed terms and relationships into the GO Cellular Component branch. Extension of GO Cellular Component branch to include terms and relationships relevant to exRNA communications Refining Gene Ontology to Include Terms and Relationships Relevant to exRNA Communications Cheung KH 1 , Laurent LC 2 , Roncaglia P 3 , Gould S 4 , Mathivanan S 5 , Hill AF 6 , Lotvall J 6 , Subramanian S 7 , Roth M 7 , Alexander R 8 , Kitchen R 1 , Rozowsky J 1 , Wauben M 9 , Quesenberry P 10 , Patel T 11 , Breakefield X 12 , Thery C 13 , Ezrin A 14 , Su A 15 , Galas D 8 , Gerstein MB 1 , Milosavljevic A 7 1 Yale University, New Haven, CT, USA; 2 UC San Diego, La Jolla, CA, USA; 3 European Bioinformatics Institute (EMBL-EBI), European Molecular Biology Laboratory, Hinxton, UK and The Gene Ontology Consortium; 4 Johns Hopkins University School of Medicine, Baltimore, MD, USA; 5 La Trobe University, Bundoora, Victoria, Australia; 6 University of Gothenburg, Gothenburg, Sweden; 7 Baylor College of Medicine, Houston, TX, USA; 8 Pacific Northwest Diabetes Research Institute, Seattle, WA, USA; 9 Universiteit Utrecht, Utrecht, Netherlands; 10 University Medicine Comprehensive Cancer Center, Providence, RI, USA; 11 Mayo Clinic, Jacksonville, FL, USA; 12 Harvard Medical School, Boston, MA, USA; 13 Institut Curie, INSERM U932, Paris, France; 14 NX PharmaGen, Louisville, KY, USA; 15 The Scripps Research Institute, La Jolla, CA, USA Abstract Add more terms and relationships that are relevant to exRNA communications Annotate metadata (metadata working group) Link to other ontologies Develop use cases for ontological data integration Future Directions GO Browser GO:1990684 protein-lipid-RNA complex definition: "A macromolecular complex containing separate protein, lipid and RNA molecules. Separate in this context means not covalently bound to each other." [GOC:vesicles, PMID:21423178, PMID:22028337, PMID:23559634] comment: Examples of protein-lipid-RNA complexes are described in PMID:21423178 and PMID:23559634, both showing evidence that high-density lipoprotein (HDL) and, to a lesser extent, low-density lipoprotein (HDL) transport endogenous microRNAs (miRNAs) and deliver them to recipient cells with functional targeting capabilities. Also see fig. 1 in the review PMID:22028337. Not to be confused with GO:0034364 'high- density lipoprotein particle' or GO:0034362 'low-density lipoprotein particle', which describe complexes of proteins and lipids only, without RNAs. synonym: "miRNA-lipoprotein complex" RELATED [] is_a: GO:0032991 ! macromolecular complex relationship: has_part CHEBI:18059 ! lipid relationship: has_part CHEBI:33697 ! ribonucleic acid relationship: has_part PR:000000001 ! protein Acknowledgements Extracellular RNA Communications Consortium External RNA Controls Consortium International Society for Extracellular Vesicles American Society for Exosomes and Microvesicles Gene Ontology Consortium This work was supported in part by NIH Common Fund Legend: Rectangles represent GO terms. Ovals represent synonyms. Arrows represent is_a relationships. Dashed lines represent synonymous relationships. White rectangles represent existing GO terms. Black arrows represent existing is_a relationships. Red markings represent either new terms/synonyms or existing terms/synonyms with new relationships.

Transcript of Refining Gene Ontology to Include Terms and Relationships Relevant to exRNA Communications

Page 1: Refining Gene Ontology to Include Terms and Relationships Relevant to exRNA Communications

An ontology is used to represent domain knowledge in a standard machine-readable way to enable data annotation, discovery, and integration. The Extracellular RNA Communication Consortium has established an ontology group to work towards standardization and classification of the terms used to describe extracellular vesicles (EVs). As part of this ontology effort, we have worked with domain experts and ontology experts to propose new terms and relationships that can be added to the widely-used Gene Ontology (GO) for describing EVs and other exRNA-containing particles. Our proposal reflects broad community consensus, as it was reviewed and approved by: • International Society for Extracellular Vesicles • American Society for Exosomes and Microvesicles. In this attempt to standardize exRNA-related terminology, we strive to strike a balance between the “lumper” and “splitter” approaches in this new and incompletely understood domain. We are currently working closely with the GO Consortium to incorporate the proposed terms and relationships into the GO Cellular Component branch.

Extension of GO Cellular Component branch to include terms

and relationships relevant to exRNA communications

Refining Gene Ontology to Include Terms and Relationships Relevant to exRNA Communications

Cheung KH1, Laurent LC2, Roncaglia P3, Gould S4, Mathivanan S5, Hill AF6, Lotvall J6, Subramanian S7, Roth M7, Alexander R8, Kitchen R1, Rozowsky J1,

Wauben M9, Quesenberry P10, Patel T11, Breakefield X12, Thery C13, Ezrin A14, Su A15, Galas D8, Gerstein MB1, Milosavljevic A7

1Yale University, New Haven, CT, USA; 2UC San Diego, La Jolla, CA, USA; 3European Bioinformatics Institute (EMBL-EBI), European Molecular Biology Laboratory, Hinxton, UK and The Gene Ontology Consortium; 4Johns Hopkins

University School of Medicine, Baltimore, MD, USA; 5La Trobe University, Bundoora, Victoria, Australia; 6University of Gothenburg, Gothenburg, Sweden; 7Baylor College of Medicine, Houston, TX, USA; 8Pacific Northwest Diabetes

Research Institute, Seattle, WA, USA; 9Universiteit Utrecht, Utrecht, Netherlands; 10University Medicine Comprehensive Cancer Center, Providence, RI, USA; 11Mayo Clinic, Jacksonville, FL, USA; 12Harvard Medical School, Boston,

MA, USA;13Institut Curie, INSERM U932, Paris, France; 14NX PharmaGen, Louisville, KY, USA; 15The Scripps Research Institute, La Jolla, CA, USA

Abstract

• Add more terms and relationships that are relevant

to exRNA communications • Annotate metadata (metadata working group) • Link to other ontologies • Develop use cases for ontological data integration

Future Directions GO Browser

GO:1990684 protein-lipid-RNA complex

definition: "A macromolecular complex containing separate

protein, lipid and RNA molecules. Separate in this context means

not covalently bound to each other." [GOC:vesicles,

PMID:21423178, PMID:22028337, PMID:23559634]

comment: Examples of protein-lipid-RNA complexes are

described in PMID:21423178 and PMID:23559634, both showing

evidence that high-density lipoprotein (HDL) and, to a lesser

extent, low-density lipoprotein (HDL) transport endogenous

microRNAs (miRNAs) and deliver them to recipient cells with

functional targeting capabilities. Also see fig. 1 in the review

PMID:22028337. Not to be confused with GO:0034364 'high-

density lipoprotein particle' or GO:0034362 'low-density lipoprotein

particle', which describe complexes of proteins and lipids only,

without RNAs.

synonym: "miRNA-lipoprotein complex" RELATED []

is_a: GO:0032991 ! macromolecular complex

relationship: has_part CHEBI:18059 ! lipid

relationship: has_part CHEBI:33697 ! ribonucleic acid

relationship: has_part PR:000000001 ! protein

Acknowledgements • Extracellular RNA Communications Consortium • External RNA Controls Consortium • International Society for Extracellular Vesicles • American Society for Exosomes and Microvesicles • Gene Ontology Consortium • This work was supported in part by NIH Common Fund

Legend:

• Rectangles represent GO terms.

• Ovals represent synonyms.

• Arrows represent is_a relationships.

• Dashed lines represent synonymous relationships.

• White rectangles represent existing GO terms.

• Black arrows represent existing is_a relationships.

• Red markings represent either new terms/synonyms or

existing terms/synonyms with new relationships.