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Towards integration of systems biology and biomedical ontologies
 

Towards integration of systems biology and biomedical ontologies

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Systems biology is an approach to biology that emphasizes the...

Systems biology is an approach to biology that emphasizes the
structure and dynamic behavior of biological systems and the
interactions that occur within them. To succeed, systems biology
crucially depends on the accessibility and integration of data across
domains and levels of granularity. Biomedical ontologies were
developed to facilitate such an integration for data and are often
used to annotate biosimulation models in systems biology.
Here, I present an approach towards combining both disciplines in a common framework that enables information to flow between both.

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    Towards integration of systems biology and biomedical ontologies Towards integration of systems biology and biomedical ontologies Presentation Transcript

    • Towards integration of systems biology and biomedical ontologies Robert Hoehndorf Department of Genetics University of Cambridge 29 March 2011Robert Hoehndorf (University of Cambridge) Harvesting SBML 29 March 2011 1 / 28
    • Introduction Motivation MotivationRobert Hoehndorf (University of Cambridge) Harvesting SBML 29 March 2011 2 / 28
    • Introduction Motivation MotivationRobert Hoehndorf (University of Cambridge) Harvesting SBML 29 March 2011 3 / 28
    • Introduction Ontology Applied ontology ontology (philosophy) studies the nature of existence and categories of being an ontology (computer science) is the “explicit specification of a conceptualization of a domain” [Gruber, 1993] ontologies specify the meaning of terms in a vocabulary formalized ontologies can be used by computers and automated systems Applied ontology is the branch of knowledge representation that focuses on the content.Robert Hoehndorf (University of Cambridge) Harvesting SBML 29 March 2011 4 / 28
    • Introduction Ontology Open Biomedical Ontologies (OBO) Individual Physical object Quality Function Process ChEBI Ontology Molecule Gene Sequence Ontology Transcript GO-CC Organelle Celltype Gene Ontology Cell Phenotype Tissue Ontology Organ Anatomy Ontology Body PopulationRobert Hoehndorf (University of Cambridge) Harvesting SBML 29 March 2011 5 / 28
    • Introduction Ontology Systems biology Systems biology...is about putting together rather than taking apart, integration rather than reduction. [Denis Noble] multi-scale data integration domains and levels of granularity species kinds of data integration of in silico, in vitro and in vivo research focus on emergent properties simulation of biological systems predict and simulate systems’ behaviorRobert Hoehndorf (University of Cambridge) Harvesting SBML 29 March 2011 6 / 28
    • Introduction Ontology Systems biology Challenges (Kitano, 2002) data integration validation standard languages specification exchange resultsRobert Hoehndorf (University of Cambridge) Harvesting SBML 29 March 2011 7 / 28
    • Introduction Ontology Systems biology Challenges (Kitano, 2002) data integration validation standard languages specification exchange results Can we use ontologies to address these problems?Robert Hoehndorf (University of Cambridge) Harvesting SBML 29 March 2011 7 / 28
    • Harvesting SBML MIRIAM annotations Annotation of SBMLRobert Hoehndorf (University of Cambridge) Harvesting SBML 29 March 2011 8 / 28
    • Harvesting SBML MIRIAM annotations Annotation of SBML MIRIAM provides annotation of SBML entities ontologies are treated as meta-data search semantic similarity documentation no integration with modelling languageRobert Hoehndorf (University of Cambridge) Harvesting SBML 29 March 2011 9 / 28
    • Harvesting SBML MIRIAM annotations Information flow hypothesis Integration of SBML and ontologies could lead to information flow between models and ontologies. Information flow enables the use of ontologies for verification, access to data, integration and combination of models.Robert Hoehndorf (University of Cambridge) Harvesting SBML 29 March 2011 10 / 28
    • Harvesting SBML MIRIAM annotationsRobert Hoehndorf (University of Cambridge) Harvesting SBML 29 March 2011 11 / 28
    • Harvesting SBML Ontological commitment Rule 1: models Model M annotated with A1: M represents an object O1 O1 can have functions O1 ’s functions can be realized by processes model components represent parts of O1 M SubClassOf: represents some A1 M SubClassOf: represents some (has-function some A1) M SubClassOf: represents some (has-function some (realized-by only A1)Robert Hoehndorf (University of Cambridge) Harvesting SBML 29 March 2011 12 / 28
    • Harvesting SBML Ontological commitment BioModel 82 annotated with heterotrimeric G-protein complex cycle (GO:0031684): represents an object O1 O1 has a function F1 F1 is realized by processes of the type heterotrimeric G-protein complex cycle M SubClassOf: represents some O1 O1 SubClassOf: (has-function some (realized-by only GO:0031684)Robert Hoehndorf (University of Cambridge) Harvesting SBML 29 March 2011 13 / 28
    • Harvesting SBML Ontological commitment Rule 2: Compartments Compartment C annotated with A2: represents an object O2 part of the O1 compartment’s species represent objects that are located in O2 C SubClassOf: represents some A2 A2 SubClassOf: located-in some A1Robert Hoehndorf (University of Cambridge) Harvesting SBML 29 March 2011 14 / 28
    • Harvesting SBML Ontological commitment Compartment “Cell” in BioModel 82 annotated with Cell (GO:0005623): represents an object O2 O2 is a kind of Cell O2 is part-of O1 C SubClassOf: represents some O2 O2 SubClassOf: Cell and part-of some O1Robert Hoehndorf (University of Cambridge) Harvesting SBML 29 March 2011 15 / 28
    • Harvesting SBML Ontological commitment Compartment “Cell” in BioModel 82 annotated with Cell (GO:0005623): represents an object O2 O2 is a kind of Cell O2 is part-of O1 C SubClassOf: represents some O2 O2 SubClassOf: Cell and part-of some O1 O2 SubClassOf: Cell and part-of some (has-function some (realized-by only GO:0031684))Robert Hoehndorf (University of Cambridge) Harvesting SBML 29 March 2011 15 / 28
    • Harvesting SBML Ontological commitment Rule 3: Species represents an object O3 O3 can have functions O3 ’s functions can be realized by processes O3 can have qualities (concentration, amount, charge,...) located in O2Robert Hoehndorf (University of Cambridge) Harvesting SBML 29 March 2011 16 / 28
    • Harvesting SBML Ontological commitment Species GTP in “Cell” in BioModel 82 annotated with GTP (CHEBI:15996): represents an object O3 O3 is a kind of GTP O3 is located-in O2 S SubClassOf: represents some O3 O3 SubClassOf: GTP and located-in some O2 O3 SubClassOf: GTP and located-in some (Cell and part-of some (has-function some (realized-by only GO:0031684)))Robert Hoehndorf (University of Cambridge) Harvesting SBML 29 March 2011 17 / 28
    • Harvesting SBML Ontological commitment Reaction represents an object O3 with a function F F is realized by P P has participants (inputs, outputs and modifiers) O4 O4 are objects represented by species P occurs in O1Robert Hoehndorf (University of Cambridge) Harvesting SBML 29 March 2011 18 / 28
    • Harvesting SBML Ontological commitment Reaction GTP-binding in BioModel 82 annotated with GTP binding (GO:0005525): represents an object O4 O4 has a function F4 F4 is a kind of GTP binding F4 is realized by P4 P4 has-input O3 (GTP) R SubClassOf: represents some (has-function some F4) F4 SubClassOf: GTP binding and realized-by only P P SubClassOf: has-input some O3Robert Hoehndorf (University of Cambridge) Harvesting SBML 29 March 2011 19 / 28
    • Harvesting SBML Ontological commitment Reaction GTP-binding in BioModel 82 World of BIOMD0000000082 BIOMD0000000082 - Thomsen1988 AdenylateCyclase Inhibition has-function (realized-by) heterotrimeric G-protein complex cycle Cell in Compartment "cell" represents World of BIOMD0000000082 has-part Cell part-of DRG GDP GTP has-part GTP binding in world of World of BIOMD0000000082 BIOMD0000000082 has-part GTP represents GTP part-of Cell in World of Reactions BIOMD0000000082 Reaction: GTP binding with DRG represents GTP binding in world of BIOMD0000000082 represents* has-input ParameterRobert Hoehndorf (University of Cambridge) Harvesting SBML 29 March 2011 20 / 28
    • Harvesting SBML Ontological commitment BioModels Result Ontologies: FMA ChEBI GO Celltype PATO (KEGG, Reactome) Result on BioModels: more than 300,000 classes more than 800,000 axioms 90,000 complex model annotations http://sbmlharvester.googlecode.comRobert Hoehndorf (University of Cambridge) Harvesting SBML 29 March 2011 21 / 28
    • Harvesting SBML Inconsistency Compartments/species annotated with functions or processesRobert Hoehndorf (University of Cambridge) Harvesting SBML 29 March 2011 22 / 28
    • Harvesting SBML Inconsistency Biological inconsistency: Biomodel 176Robert Hoehndorf (University of Cambridge) Harvesting SBML 29 March 2011 23 / 28
    • Harvesting SBML Inconsistency Biological inconsistency: Biomodel 176 [Term] id: GO:0016887 name: ATPase activity is a: GO:0017111 ! nucleoside-triphosphatase activity intersection of: GO:0003824 ! catalytic activity intersection of: has input CHEBI:15377 ! water intersection of: has input CHEBI:15422 ! ATP intersection of: has output CHEBI:16761 ! ADP intersection of: has output CHEBI:26020 ! phosphatesRobert Hoehndorf (University of Cambridge) Harvesting SBML 29 March 2011 24 / 28
    • Harvesting SBML Knowledge retrieval Query Query string # results Contradictory defined entities Nothing 4,899 Models which represent a pro- model-of some (has-part some (has-function 54 cess involving sugar some (realized-by only (has-participant some sugar)))) Parts of BIOMD0000000015 that part-of some BIOMD0000000015 and represents 29 represent processes involving some (has-function some (realized-by only sugar (has-participant some sugar))) Model entities that represent the represents some (has-part some (has-function 14 cell cycle some (realized-by only ’cell cycle’))) Model entities that represent represents some (has-part some (’has role’ 2 mutagenic central nervous sys- some ’central nervous system drug’ and tem drugs in the gastrointestinal ’has role’ some mutagen and part-of some systems ’Gastrointestinal system’) Model entities that represent represents some (has-function some 4 catalytic activity involving sugar (realized-by only (realizes some ’catalytic in the endocrine pancreas activity’ and has-participant some (sugar and contained-in some (part-of some ’Endocrine pancreas’)))))Robert Hoehndorf (University of Cambridge) Harvesting SBML 29 March 2011 25 / 28
    • Conclusions Future research Towards integration of systems biology and biomedical ontology extension to other modelling frameworks (CellML, FieldML, ...) application to other resources YeastNet knowledge discovery ontology of functions (of chemicals) model comparison model compositionRobert Hoehndorf (University of Cambridge) Harvesting SBML 29 March 2011 26 / 28
    • Conclusions Acknowledgements George Gkoutos Michel Dumontier Dan Cook Bernard de Bono John Gennari Pierre Grenon Sarala WimalaratneRobert Hoehndorf (University of Cambridge) Harvesting SBML 29 March 2011 27 / 28
    • Conclusions Thank you! Biomodels, YeastNet in OWL: http://sbmlharvester.googlecode.com Modularization: http://el-vira.googlecode.comRobert Hoehndorf (University of Cambridge) Harvesting SBML 29 March 2011 28 / 28