# Presentation: 128109

## The OBO Foundry

- Barry Smith
- University at Buffalo
- http://ontology.buffalo.edu/smith

- Ontology: A Vision for the Future and Its Realization

## 

how do we know what data we have ?
how do I know what data you have ?
how do we know what data we don’t have ?
how do we make different sorts of data combinable, as we need to do in large domains such as neurodevelopment, immunology, cancer ...?

- how do we know *what *data we have ?
- how do *I* know what data *you *have ?
- how do we know what data we *don’t *have ?
- how do we make different sorts of data *combinable, *as we need to do in large domains such as neurodevelopment, immunology, cancer ...?

**we are accumulating huge amounts of ****sequence data, image data, pharma data, ...**

## 

genomic medicine, molecular medicine, translational medicine, personalized medicine ... need
methods for data integration to enable reasoning across data at multiple granularities

**genomic medicine, molecular medicine, translational medicine, personalized medicine ... need**
**methods for data integration to enable reasoning across data at multiple granularities**

- to identify **biomedically relevant relations **on the side of the entities themselves

## Slide 4

## = we need ontologies

***where in the body *****?**

**what kind of *****disease process *****?**

**= we need ontologies**

**we need *****semantic***** annotation of data**

**Notes:**
dir.niehs.nih.gov/ microarray/datamining/ 

## 
Semantic Web, Moby, wikis, etc.
let a million flowers (and weeds) bloom
to create integration rely on (automatically generated?) post hoc mappings

- Semantic Web, Moby, wikis, etc.
- let a million flowers (and weeds) bloom
- to create integration rely on (automatically generated?) ***post hoc***** mappings**

- how create broad-coverage semantic annotation systems for biomedicine?

##    most successful, thus far: UMLS

- built by trained experts
- massively useful for information retrieval and information integration
- UMLS Metathesaurus a system of ***post hoc *****mappings between source vocabularies separately built**

## UMLS-based mappings fall shortof creating interoperability

- because local usage is respected
- regimentation frowned upon, no concern for cross-framework consistency
- UMLS terminologies have different grades of formal rigor, different degrees of completeness, different update policies

## with UMLS-based annotations

- we can know *what data we have* (via term searches), but it is noisy
- we can *map between data at single granularities* (via ‘synonyms’), but synonymy information is noisy
- how do we know what data we *don’t* have ?
- how do we *reason* with data (as at the molecular level), when no common logical backbone ?

## for science

- to develop high quality annotation resources in a collaborative, community effort?
- create an evolutionary path towards improvement of terminologies, of the sort we find elsewhere in science
- find ways to reward early adopters of the results

- what is to be done?

## for science

- science works out from a consensus core, and strives to isolate and resolve inconsistencies as it extends at the fringes
- 	we need to create a consensus core
- start with what for human beings are trivialities (low hanging fruit) and work out from there

- for science, *consistency* is a *sine qua non*

## part_of 

***Pleural ***
***Cavity***

***Interlobar ***
***recess***

***Mesothelium ***
***of Pleura***

***Pleura(Wall ***
***of Sac)***

***Visceral***
***Pleura***

***Pleural Sac***

***Parietal ***
***Pleura***

**Anatomical Space**

**Organ**
**Cavity**

**Serous Sac**
**Cavity**

**Anatomical**
**Structure**

**Organ**

***Serous Sac***

***Mediastinal***
***Pleura***

**Tissue**

**Organ **
**Component**

**Organ Cavity**
**Subdivision**

**Serous Sac**
**Cavity**
**Subdivision**

***part_of ***

***is_a ***

**Foundational Model of Anatomy**

## for science

- include ontologies corresponding to the basic biomedical sciences in the core

- clinical medicine relies on anatomy
- and molecular biology to provide
- integration across medical specialisms

## for science

- where do we find scientifically validated information linking gene products and other entities represented in biochemical databases to semantically meaningful terms pertaining to disease, anatomy, development, histology in different model organisms?

- but we need more

**Notes:**
Woops: 54M already ! Compare with 3M Dec 2004, and 12 M june 2005 when I did this. 

**what makes GO so wildly successful ?**

## science basis of the GO: trained experts curating peer-reviewed literature
different model organism databases employ scientific curators who use the experimental observations reported in the biomedical literature to associate GO terms with gene products in a coordinated way 

- different model organism databases employ scientific curators who use the experimental observations reported in the biomedical literature to associate GO terms with gene products in a coordinated way

- The methodology of annotations

## cellular locations
molecular functions
biological processes 
used to annotate the entities represented in the major biochemical databases
thereby creating integration across these databases and making them available to semantic search

- molecular functions
- biological processes
- used to annotate the entities represented in the **major biochemical databases**
- thereby creating integration across these databases and making them available to semantic search

- A set of standardized textual descriptions of

## what cellular component?

**what cellular component?**

**what molecular function?**

**what biological process?**

**Notes:**
dir.niehs.nih.gov/ microarray/datamining/ 

## This process

- leads to improvements and extensions of the ontology
- which in turn leads to better annotations
-  a virtuous cycle of improvement in the quality and reach of both future annotations and the ontology itself
- RESULT: a slowly growing computer-interpretable map of biological reality within which **major databases are automatically integrated in semantically searchable form**

## Five bangs for your GO buck

**science base**
**cross-species database integration**
**cross-granularity database integration**
***through***** links to the things which are of biomedical relevance**
****** ****semantic searchability links people to software**

## but now

- need to improve the quality of GO to support more rigorous logic-based reasoning across the data annotated in its terms
- need to extend the GO by engaging ever broader community support for the addition of new terms and for the correction of errors

## but also

- need to extend the methodology to other domains, including clinical domains  need for
- 	disease ontology
- 	immunology ontology
- 	symptom (phenotype) ontology
- 	clinical trial ontology ...

## the problem

- existing clinical vocabularies are of variable quality and low mutual consistency
- need for *prospective standards* to ensure mutual consistency and high quality of clinical counterparts of GO
- need to ensure consistency of the new clinical ontologies with the basic biomedical sciences
- if we do not start now, the problem will only get worse

## the solution

- establish common rules governing best practices for creating ontologies and for using these in annotations
- apply these rules to create a complete suite of orthogonal interoperable biomedical reference ontologies
- this solution is already being implemented

## a shared portal for (so far) 58 ontologies 
(low regimentation)

http://obo.sourceforge.net  NCBO BioPortal

- (low regimentation)
- _[http://obo.sourceforge.net](http://obo.sourceforge.net/)__ _ NCBO BioPortal

**First step (2003)**

## Slide 28

## Second step (2004)reform efforts initiated, e.g. linking GO to other OBO ontologies to ensure orthogonality

- GO

- Cell type

- New Definition

**+**

**=**

- Osteoblast differentiation: Processes whereby an osteoprogenitor cell or a cranial neural crest cell acquires the specialized features of an osteoblast, a bone-forming cell which secretes extracellular matrix.

## The OBO Foundryhttp://obofoundry.org/

**The OBO Foundry****http://obofoundry.org/**

**Third step (2006)**

**Notes:**
Why suddenly the switch from deep-hell black background to heavenly white ? Is that an intended connotation or just a copy and paste coincidence?

## a family of interoperable gold standard biomedical reference ontologies to serve the annotation of inter alia
	scientific literature 
	model organism databases 
	clinical trial data 

- 	scientific literature
- 	model organism databases
- 	clinical trial data

**The OBO Foundry**

**The OBO Foundry**** ****http://obofoundry.org/**

## A prospective standard

- designed to guarantee interoperability of ontologies from the very start (contrast to: *post hoc *mapping)
- established March 2006
- 12 initial candidate OBO ontologies – focused primarily on basic science domains
- several being constructed *ab initio*
- by influential consortia who have the authority to impose their use on large parts of the relevant communities.

## GO Gene Ontology
ChEBI Chemical Ontology 
CL Cell Ontology
FMA Foundational Model of Anatomy
PaTO Phenotype Quality Ontology
SO Sequence Ontology

CARO Common Anatomy Reference Ontology 
CTO Clinical Trial Ontology
FuGO Functional Genomics Investigation Ontology
PrO Protein Ontology 
RnaO RNA Ontology 
RO Relation Ontology

- 						new

**GO Gene Ontology**
**ChEBI Chemical Ontology **
**CL Cell Ontology**
**FMA Foundational Model of Anatomy**
**PaTO Phenotype Quality Ontology**
**SO Sequence Ontology**
**CARO Common Anatomy Reference Ontology **
**CTO Clinical Trial Ontology**
**FuGO Functional Genomics Investigation Ontology**
**PrO Protein Ontology **
**RnaO RNA Ontology **
**RO Relation Ontology**

**The OBO Foundry**** ****http://obofoundry.org/**

## Slide 34

| Ontology | Scope | URL | Custodians |
| --- | --- | --- | --- |
| Cell Ontology 
(CL) | cell types from prokaryotes 
to mammals | obo.sourceforge.net/cgi-
bin/detail.cgi?cell | Jonathan Bard, Michael 
Ashburner, Oliver Hofman |
| Chemical Entities of Bio-
logical Interest (ChEBI) | molecular entities | ebi.ac.uk/chebi | Paula Dematos,
Rafael Alcantara |
| Common Anatomy Refer-
ence Ontology (CARO) | anatomical structures in 
human and model organisms | (under development) | Melissa Haendel, Terry 
Hayamizu, Cornelius Rosse, 
David Sutherland,  |
| Foundational Model of Anatomy (FMA) | structure of the human body | fma.biostr.washington.
edu | JLV Mejino Jr.,
Cornelius Rosse |
| Functional Genomics 
Investigation Ontology 
(FuGO) | design, protocol, data 
instrumentation, and analysis | fugo.sf.net | FuGO Working Group |
| Gene Ontology 
(GO) | cellular components, 
molecular functions, 
biological processes | www.geneontology.org | Gene Ontology Consortium |
| Phenotypic Quality 
Ontology 
(PaTO) | qualities of anatomical 
structures | obo.sourceforge.net/cgi
-bin/ detail.cgi?
attribute_and_value | Michael Ashburner, Suzanna 
Lewis, Georgios Gkoutos |
| Protein Ontology 
(PrO) | protein types and 
modifications | (under development) | Protein Ontology Consortium |
| Relation Ontology (RO) | relations | obo.sf.net/relationship | Barry Smith, Chris Mungall |
| RNA Ontology
(RnaO) | three-dimensional RNA 
structures | (under development) | RNA Ontology Consortium |
| Sequence Ontology
(SO) | properties and features of 
nucleic sequences | song.sf.net | Karen Eilbeck |

|                     RELATION
                TO TIME 

 GRANULARITY | CONTINUANT |  |  |  | OCCURRENT |
| --- | --- | --- | --- | --- | --- |
|  | INDEPENDENT |  | DEPENDENT |  |  |
| ORGAN AND
ORGANISM | Organism
(NCBI
Taxonomy?) | Anatomical Entity
(FMA, CARO) | Organ
Function
(FMP, CPRO) | Phenotypic Quality(PaTO) | Organism-Level Process
(GO) |
| CELL AND CELLULAR COMPONENT | Cell
(CL) | Cellular Component
(FMA, GO) | Cellular Function
(GO) |  | Cellular Process
(GO) |
| MOLECULE | Molecule
(ChEBI, SO,
RnaO, PrO) |  | Molecular Function
(GO) |  | Molecular Process
(GO) |

- Annotations plus ontologies yield an ever-growing computer-interpretable map of biological reality.

## Building out from the original GO

|                     RELATION
                TO TIME 

 GRANULARITY | CONTINUANT |  |  |  | OCCURRENT |
| --- | --- | --- | --- | --- | --- |
|  | INDEPENDENT |  | DEPENDENT |  |  |
| ORGAN AND
ORGANISM | Organism
(NCBI
Taxonomy?) | Anatomical Entity
(FMA, CARO) | Organ
Function
(FMP, CPRO) | Phenotypic Quality(PaTO) | Biological Process
(GO) |
| CELL AND CELLULAR COMPONENT | Cell
(CL) | Cellular Component
(FMA, GO) | Cellular Function
(GO) |  |  |
| MOLECULE  | Molecule
(ChEBI, SO,
RnaO, PrO) |  | Molecular Function
(GO) |  | Molecular Process
(GO) |

## Disease Ontology (DO)
Biomedical Image Ontology (BIO)
Upper Biomedical Ontology (OBO UBO)
Environment Ontology (EnvO)
Systems Biology Ontology (SBO)

- Biomedical Image Ontology (BIO)
- Upper Biomedical Ontology (OBO UBO)
- Environment Ontology (EnvO)
- Systems Biology Ontology (SBO)

- Under consideration:

**The OBO Foundry**** ****http://obofoundry.org/**

## OBO Foundry = a subset of OBO ontologies, whose developers have agreed in advance to accept a common set of principles reflecting best practice in ontology development designed to ensure 
	tight connection to the biomedical basic sciences
	compatibility
	interoperability, common relations
	formal robustness 
	support for logic-based reasoning

- 	tight connection to the biomedical basic sciences
- 	compatibility
- 	interoperability, common relations
- 	formal robustness
- 	support for logic-based reasoning

**The OBO Foundry**** ****http://obofoundry.org/**

## CRITERIA

- The ontology is OPEN and available to be used by all.
- The ontology is in, or can be instantiated in, a COMMON FORMAL LANGUAGE.
- The developers of the ontology agree in advance to COLLABORATE with developers of other OBO Foundry ontology where domains overlap.

**CRITERIA**

**The OBO Foundry**** ****http://obofoundry.org/**

## CRITERIA

**CRITERIA**

- UPDATE: The developers of each ontology commit to its maintenance in light of scientific advance, and to soliciting community feedback for its improvement.
- ORTHOGONALITY: They commit to working with other Foundry members to ensure that, for any particular domain, there is community convergence on a single controlled vocabulary.

**The OBO Foundry**** ****http://obofoundry.org/**

## for science

- if we annotate a database or body of literature with one high-quality biomedical ontology, we should be able to add annotations from a second such ontology without conflicts

**orthogonality of ontologies implies additivity of annotations**

**The OBO Foundry**** ****http://obofoundry.org/**

## CRITERIA

- IDENTIFIERS: The ontology possesses a unique identifier space within OBO.
- VERSIONING: The ontology provider has procedures for identifying distinct successive versions to ensure BACKWARDS COMPATIBITY with annotation resources already in common use
- The ontology includes TEXTUAL DEFINITIONS and where possible equivalent formal definitions of its terms.

**CRITERIA**

## CLEARLY BOUNDED: The ontology has a clearly specified and clearly delineated content.
DOCUMENTATION: The ontology is well-documented.
USERS: The ontology has a plurality of independent users.

- DOCUMENTATION: The ontology is well-documented.
- USERS: The ontology has a plurality of independent users.

**CRITERIA**

**The OBO Foundry**** ****http://obofoundry.org/**

## COMMON ARCHITECTURE: The ontology uses relations which are unambiguously defined following the pattern of definitions laid down in the OBO Relation Ontology.*

	* Smith et al., Genome Biology 2005, 6:R46

- 	*** Smith et al., *****Genome Biology *****2005, 6:R46**

**CRITERIA**

**The OBO Foundry**** ****http://obofoundry.org/**

## OBO Relation Ontology

| Foundational  | is_a
part_of |
| --- | --- |
| Spatial | located_in
contained_in
adjacent_to |
| Temporal | transformation_of
derives_from
preceded_by |
| Participation  | has_participant
has_agent |

**OBO Relation Ontology**

**The OBO Foundry**** ****http://obofoundry.org/**

## Further criteria will be added over time in light of lessons learned in order to bring about a gradual improvement in the quality of Foundry ontologies 
ALL FOUNDRY ONTOLOGIES WILL BE SUBJECT TO CONSTANT UPDATE IN LIGHT OF SCIENTIFIC ADVANCE

- ALL FOUNDRY ONTOLOGIES WILL BE SUBJECT TO CONSTANT UPDATE IN LIGHT OF SCIENTIFIC ADVANCE

**IT WILL GET HARDER**

**The OBO Foundry**** ****http://obofoundry.org/**

## But not everyone needs to join
The Foundry is not seeking to serve as a check on flexibility or creativity
ALL FOUNDRY ONTOLOGIES WILL ENCOURAGE COMMUNITY CRITICISM, CORRECTION AND EXTENSION WITH NEW TERMS

- The Foundry is not seeking to serve as a check on flexibility or creativity
- ALL FOUNDRY ONTOLOGIES WILL ENCOURAGE COMMUNITY CRITICISM, CORRECTION AND EXTENSION WITH NEW TERMS

**IT WILL GET HARDER**

**The OBO Foundry**** ****http://obofoundry.org/**

## to introduce some of the features of SCIENTIFIC PEER REVIEW into biomedical ontology development
CREDIT for high quality ontology development work
KUDOS for early adopters of high quality ontologies / terminologies e.g. in reporting clinical trial results

- CREDIT for high quality ontology development work
- KUDOS for early adopters of high quality ontologies / terminologies e.g. in reporting clinical trial results

**GOALS**

**The OBO Foundry**** ****http://obofoundry.org/**

## to providing a FRAMEWORK OF RULES to counteract the current policy of ad hoc creation of new annotation schemas by each clinical research group by
REUSABILITY: if data-schemas are formulated using a single well-integrated framework ontology system in widespread use, then this data will be to this degree itself become more widely accessible and usable

- REUSABILITY: if data-schemas are formulated using a single well-integrated framework ontology system in widespread use, then this data will be to this degree itself become more widely accessible and usable

**GOALS**

**The OBO Foundry**** ****http://obofoundry.org/**

## to serve as BENCHMARK FOR IMPROVEMENTS in discipline-focused terminology resources
once a system of interoperable reference ontologies is there, it will make sense to calibrate existing terminologies in its terms in order to achieve more robust alignment and greater domain coverage
exploit the avenue of EVIDENCE-BASED MEDICINE (NIH CLINICAL RESEARCH NETWORKS) to foster their use by clinicians 

- once a system of interoperable reference ontologies is there, it will make sense to calibrate existing terminologies in its terms in order to achieve more robust alignment and greater domain coverage
- exploit the avenue of EVIDENCE-BASED MEDICINE (NIH CLINICAL RESEARCH NETWORKS) to foster their use by clinicians

**GOALS**

**The OBO Foundry**** ****http://obofoundry.org/**

## 	
	June 2006: establishment of MICheck:
	reflects growing need for prescriptive checklists specifying the key information to include when reporting experimental results (concerning methods, data, analyses and results). 

- 	June 2006: establishment of MICheck:
- 	reflects growing need for prescriptive checklists specifying the key information to include when reporting experimental results (concerning methods, data, analyses and results).

**the vision is spreading**

**The OBO Foundry**** ****http://obofoundry.org/**

## MICheck: ‘a common resource for minimum information checklists’ analogous to OBO / NCBO BioPortal
MICheck Foundry: will create ‘a suite of self-consistent, clearly bounded, orthogonal, integrable checklist modules’ * 
	* Taylor CF, et al. Nature Biotech, in press

**MICheck Foundry:** will create ‘a suite of self-consistent, clearly bounded, orthogonal, integrable checklist modules’ *
**	***** Taylor CF, et al. *****Nature Biotech*****, in press**

**MICheck Foundry**

**The OBO Foundry**** ****http://obofoundry.org/**

## Transcriptomics (MIAME Working Group)
Proteomics (Proteomics Standards Initiative)
Metabolomics (Metabolomics Standards Initiative)
Genomics and Metagenomics (Genomic Standards Consortium)
In Situ Hybridization and Immunohistochemistry (MISFISHIE Working Group)
Phylogenetics (Phylogenetics Community) 
RNA Interference (RNAi Community) 
Toxicogenomics (Toxicogenomics WG) 
Environmental Genomics (Environmental Genomics WG)
Nutrigenomics (Nutrigenomics WG)
Flow Cytometry (Flow Cytometry Community)

**Transcriptomics** (MIAME Working Group)
**Proteomics** (Proteomics Standards Initiative)
**Metabolomics** (Metabolomics Standards Initiative)
**Genomics and Metagenomics** (Genomic Standards Consortium**)**
***In Situ***** Hybridization and Immunohistochemistry** (MISFISHIE Working Group)
**Phylogenetics** (Phylogenetics Community)
**RNA Interference** (RNAi Community)
**Toxicogenomics** (Toxicogenomics WG)
**Environmental Genomics **(Environmental Genomics WG)
**Nutrigenomics (**Nutrigenomics WG)
**Flow Cytometry** (Flow Cytometry Community)

**MICheck/Foundry communities**

## 	how to replicate the successes of the GO in clinical medicine?
	choose two or three representative disease domains
	work out reasoning challenges for those domains
	work with specialists to create ontologies interoperable with OBO Foundry basic science ontologies to address these reasoning challenges
	work with leaders of professional associations and of clinical trial initiatives to foster the collection of clinical data annotated in their terms

- 	how to replicate the successes of the GO in clinical medicine?
- 	choose two or three representative disease domains
- 	work out reasoning challenges for those domains
- 	work with specialists to create ontologies interoperable with OBO Foundry basic science ontologies to address these reasoning challenges
- 	work with leaders of professional associations and of clinical trial initiatives to foster the collection of clinical data annotated in their terms

**Fourth Step (the future)**

## OBO Foundry coverage 

|  

  | CONTINUANT |  |  |  | OCCURRENT |
| --- | --- | --- | --- | --- | --- |
|  | INDEPENDENT |  | DEPENDENT |  |  |
| ORGAN AND
ORGANISM | Organism
(NCBI
Taxonomy?) | Anatomical Entity
(FMA, CARO) | Organ
Function
(FMP, CPRO) | Phenotypic Quality(PaTO) | Organism-Level Process
(GO) |
| CELL AND CELLULAR COMPONENT | Cell
(CL) | Cellular Component
(FMA, GO) | Cellular Function
(GO) |  | Cellular Process
(GO) |
| MOLECULE | Molecule
(ChEBI, SO,
RnaO, PrO) |  | Molecular Function
(GO) |  | Molecular Process
(GO) |

- OBO Foundry coverage
- (canonical ontologies)

| INDEPENDENT
CONTINUANTS |
| --- |
| organism |
| system |
| organ |
| organ part |
| tissue |
| cell |
| acellular anatomical structure |
| biological molecule |
| genome |

| DEPENDENT CONTINUANTS |  |  |  |
| --- | --- | --- | --- |
| physiology
(functions) | pathology |  |  |
|  | acute stage | progressive stage | resolution stage |

## Draft Ontology for Acute Respiratory Distress Syndrome

## Draft Ontology for Muscular Sclerosis

**Draft Ontology for Muscular Sclerosis**

## Draft Ontology for Muscular Sclerosis

**Draft Ontology for Muscular Sclerosis**

**to apprehend what is unknown requires a *****complet*****e demarcation of the relevant space of alternatives**

** **

** **

## with thanks (inter alia) to

- with thanks (*inter alia*) to

| Michael Ashburner
Carol Bean
Judy Blake
OIivier Bodenreider
William Bug
Werner Ceusters
Lindsay Cowell
Louis Goldberg
Frank Hartel
David Hill
Anand Kumar | Suzi Lewis
Jane Lomax 
Onard Mejino
Chris Mungall
Mark Musen + NCBO Team 
Fabian Neuhaus
Alan Rector
Cornelius Rosse
Karen Skinner
Kent Spackman
University at Buffalo |
| --- | --- |