Técnicas de IA para Biologia

9 - OBO Language and Gene Ontology

André Lamúrias

OBO Language and Gene Ontology

OBO Language

OBO Language

Overview

  • Open Biomedical Ontologies (OBO) Language
  • Developed by the Gene Ontology (GO) Consortium
  • Main target the GO
  • Adopted by numerous bio-ontologies
  • Subset of the semantics of OWL 2 language

OBO Language

OBO Ontologies

  • Composed of
    • A header
      • Provides information about the ontology
    • A set of stanzas
      • Correspond to the content of the ontology

OBO Language

OBO header

  • Information about
    • Format
    • Version date
    • Subsetdef indications - Slims
      • top-level terms
    • Synonyms
    • Name
    • Metaproperties

OBO Language

OBO header Example

  • Gene Ontology
format-version: 1.2
data-version: releases/2023-04-01
subsetdef: chebi_ph7_3 "Rhea list of ChEBI terms representing the major species
     at pH 7.3."
subsetdef: gocheck_do_not_annotate "Term not to be used for direct annotation"
...
subsetdef: goslim_yeast "Yeast GO slim"
synonymtypedef: syngo_official_label "label approved by the SynGO project"
synonymtypedef: systematic_synonym "Systematic synonym" EXACT
default-namespace: gene_ontology
ontology: go
property_value: http://purl.org/dc/elements/1.1/description "The Gene Ontology
     (GO) provides a framework and set of concepts for describing the functions
     of gene products from all organisms." xsd:string
property_value: http://purl.org/dc/elements/1.1/title "Gene Ontology" xsd:string
property_value: http://purl.org/dc/terms/license http://creativecommons.org/
     licenses/by/4.0/
property_value: owl:versionInfo "2023-04-01" xsd:string

OBO Language

OBO stanzas

  • Contain key-value lines
  • Refer to
    • Universal types - classes/concepts - ($\sf [Term]$)
    • Type definitions - properties/roles - ($\sf [TypeDef]$)
    • Instances - objects/individuals - ($\sf [Instance]$)
  • Classified into namespaces
    • For GO:
      • Molecular function
      • Biological process
      • Cellular component

OBO Language

OBO stanzas

  • Alternative identifiers
  • Definition of the item
    • with reference to the source(s)/author(s)
  • Subsets to which this item belongs
  • Different semantic links
    • Synonyms
    • External references
    • Relations between terms
    • Logical definitions
  • Comments indicated with !

OBO Language

OBO stanzas - Example

[Term]
id: GO:0000003
name: reproduction
namespace: biological_process
alt_id: GO:0019952
alt_id: GO:0050876
def: "The production of new individuals that contain some portion of genetic
     material inherited from one or more parent organisms." [GOC:go_curators,
     GOC:isa_complete, GOC:jl, ISBN:0198506732]
subset: goslim_agr
subset: goslim_chembl
subset: goslim_flybase_ribbon
subset: goslim_pir
subset: goslim_plant
synonym: "reproductive physiological process" EXACT []
xref: Wikipedia:Reproduction
is_a: GO:0008150 ! biological_process
disjoint_from: GO:0044848 ! biological phase

OBO Language

OBO stanzas - Example

  • Also definitions of relations
[Typedef]
id: part_of
name: part of
namespace: external
xref: BFO:0000050
is_transitive: true
inverse_of: has_part ! has part

OBO Language

OBO stanzas - Example

  • Such definitions can be used in other stanzas
[Term]
id: GO:0000139
name: Golgi membrane
namespace: cellular_component
def: "The lipid bilayer surrounding any of the compartments of the Golgi
   apparatus." [GOC:mah]
is_a: GO:0098588 ! bounding membrane of organelle
relationship: part_of GO:0005794 ! Golgi apparatus

OBO Language

Logical relations

  • Subclasses - $\sf is\_a$
  • Class Disjointness - $\sf disjoint\_from$
  • Property characteristics
    • Transitivity - $\sf is\_transitive$
    • Inverse properties - $\sf inverse\_of$
  • Logical definitions
    • Set of lines starting with $\sf intersection\_of$
    • Equivalent to the conjunction of these terms/representations

OBO Language

OBO stanzas - Example

  • Logical definition
[Term]
id: GO:0000019
name: regulation of mitotic recombination
namespace: biological_process
def: "Any process that modulates the frequency, rate or extent of DNA
     recombination during mitosis." [GOC:go_curators]
synonym: "regulation of recombination within rDNA repeats" NARROW []
is_a: GO:0000018 ! regulation of DNA recombination
intersection_of: GO:0065007 ! biological regulation
intersection_of: regulates GO:0006312 ! mitotic recombination
relationship: regulates GO:0006312 ! mitotic recombination

OBO Language and Gene Ontology

Gene Ontology

Gene Ontology

Overview

  • Comprehensive model of biological systems
    • From the molecular level to larger pathways, cellular and organism-level systems
  • Computational representation of scientific knowledge about the function of genes
    • Taking into considerations all possible organisms
  • Widely used to support scientific research
    • Cited in tens of thousands of publications
  • Linked to many other biomedical ontologies

Gene Ontology

Main Idea

  • Understanding gene function is one of the primary aims of biomedical research
  • Experimental knowledge obtained in one organism often applicable in others
    • If Organisms share relevant genes inherited from common ancestors
  • Gene Ontology consortium appeared in 1998 with genom studies of three model organisms
    • Drosophila melanogaster (fruit fly)
    • Mus musculus (mouse)
    • Saccharomyces cerevisiae (baker's yeast)
  • Create collaborative classification schema for gene function
    • Today extended to thousands of organisms

Gene Ontology

Usage Overview

  • Cross-species comparisons
  • Gene-expression profiling experiments
  • Automatic annotation of expression sequence tags (EST) and genomes
  • Comparative genomics
  • Network modeling
  • Analysis of semantic similarity

Gene Ontology

Three Subontologies

  • Molecular Function
    • Biochemical activity of a gene product
    • On a molecular level of granularity
    • No indication when or where event occurs (or purpose)
Term Term ID Definition
mannosyltransferase activity GO:0000030 Catalysis of the transfer of a mannosyl group to an acceptor molecule, typically another carbohydrate or a lipid
zinc binding GO:0008270 Interacting selectively and noncovalently with zinc (Zn) ions

Gene Ontology

Three Subontologies

  • Biological Process
    • Biological objective to which gene (product) contributes
    • Assemblies of molecular function, collection of events with beginning and end
    • At the level of granularity of the cell or organism
Term Term ID Definition
ossification GO:0001503 The formation of bone or of a bony substance, or the conversion of fibrious tissue or of cartilage into bone or a bony substance
regulation of glial cell proliferation GO:0060251 Any process that modulates the frequency, rate or extent of glial cell proliferation

Gene Ontology

Three Subontologies

  • Cellular Component
    • Location where gene product is active
Term Term ID Definition
Golgi apparatus GO:0005794 A compound membranous cytoplasmic organelle of eukaryotic cells, consisting of flattened, ribosome-free vesicles arranged in a more or less regular stack
viral capsid GO:0019208 The protein coat that surrounds the infective nucleic acid in some virus particles

Gene Ontology

Relations

  • Subclasses $\sf is\_a$
  • Part-whole relations $\sf part\_of$
    • E.g. nucleus is part of a cell $nucleus \sqsubseteq \exists part\_of.cell$
  • Relations between processes $\sf regulates$
    • With subrelations $positively\_regulates$ and $negatively\_regulates$
  • Whole-part relations $\sf has\_part$
    • Inverse to $\sf part\_of$
    • But the established relations are not necessary inverse
      • $$nucleus \sqsubseteq \exists has\_part. chromosome$$
      • Does not imply that every chromosome is part of a nucleus

OBO Language and Gene Ontology

Annotations

Annotations

Overview

  • Used during curation process
  • Terms of GO do not refer to specific genes
    • Rather to their characteristics
  • Annotation indicates that a GO term applies to a particular gene product
  • Biocurators read full-text articles in their area of expertise and add information to a database using structured vocabularies, such as GO

Annotations

Some Statistics for GO

  • Release April 2023
  • Number of annotations: 7,442,411
  • Number of annotated scientific publications: 173,800
  • Annotated gene products: 1,502,221
  • Annotated species: 5291

Annotations

Growth of Annoted Publications

Annotations

Terms per Subontology

Annotations

Changes in GO terms

Annotations

Annotation information

  • Gene identifier
  • GO term
  • Type of evidence to support annotation
  • reference to the evidence
  • Further complementary data (on database, synonyms, species etc.)

Annotations

Evidence for Gene Functions

  • Tradeoff between coverage and accuracy
  • Highest-quality annotations from experiments
  • Computational analyis - based on in silico analysis
    • Sequence orthology - genes in two different species have common evolutionary origin
      • E.g., because of that location/type of gene in a species can be inferred
  • Author statement evidence
    • For references to articles that refer to papers with the original research
  • Curatorial evidence based on inference by curator from GO annotations
  • ND - no biological data available

Annotations

Inferred from Electronic Annotations

  • Generated automatically, and not validated (yet)
  • Two kinds:
    • Map functional data from other databases with different but compatible vocabulary
      • E.g. UniProt in molecular biology with different goals (compared to GO)
      • MGI map UniProt keywords to GO terms to create GO annotations automatically
    • Use common origin of genes to pass annotations from well-studied organisms to less-studied organisms

Annotations

General Principles (from GO webpage)

  • Annotations represent normal functions of gene products
  • A gene product annotated to zero or more terms from each ontology
  • Each annotation supported by a GO evidence code from the evidence and conclusions ontology and a references
  • Gene products annotated to the most granular term in the ontology that is supported by available evidence
  • Annotation to a GO term implies annotation to all its parents
  • Annotations may change over time and reflect the current view
  • Open world assumption - lack of annotation - role still unknown

OBO Language and Gene Ontology

Summary

  • OBO Language
  • Gene Ontology
  • Annotations

Further reading:

  • Robinson and Bauer, Introduction to Bio-Ontologies, Chapters 4.1 and 5
  • Dessimoz and Skunca, The Gene Ontology Handbook
  • GO webpage http://geneontology.org/