an introduction to anatomy ontologies phenotype rcn feb 23 2012 n.
Download
Skip this Video
Loading SlideShow in 5 Seconds..
An Introduction to Anatomy Ontologies Phenotype RCN Feb 23, 2012 PowerPoint Presentation
Download Presentation
An Introduction to Anatomy Ontologies Phenotype RCN Feb 23, 2012

Loading in 2 Seconds...

play fullscreen
1 / 47

An Introduction to Anatomy Ontologies Phenotype RCN Feb 23, 2012 - PowerPoint PPT Presentation


  • 130 Views
  • Uploaded on

An Introduction to Anatomy Ontologies Phenotype RCN Feb 23, 2012. Melissa Haendel. Setting the stage. Who are we? What do we need? Why are we here? What is an anatomy ontology? What kinds of anatomy ontologies exist? How are anatomy ontologies used? Anatomical evidence . Who are we? .

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'An Introduction to Anatomy Ontologies Phenotype RCN Feb 23, 2012' - maren


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
setting the stage

Setting the stage

Who are we? What do we need? Why are we here?

What is an anatomy ontology?

What kinds of anatomy ontologies exist?

How are anatomy ontologies used?

Anatomical evidence

slide3

Who are we?

Domain Experts:

Anatomists, comparative morphologists,

developmental biologists, immunologists, neuroscientists, etc.

Engineers: have to build tools that can consume ontologies and give the Domain Experts the right results

Domain experts: want to query for gene expression and phenotypes across species

Ontologists: have to be able to interpret and represent domain knowledge computationally

Ontologists:

Biologists-gone-informatics, computer scientists and logicians

Engineers:

Our tool builders

we want to enable
We want to enable:
  • Comparison of structures across different organisms, scales
  • Standardization of anatomical vocabulary among and between communities
  • Integration of anatomical data across databases
  • Query across large amount of data
  • Automatic reasoning to infer related classes
  • Error checking
  • Annotation consistency

Therefore, we build ontologies that are intelligible to:

Engineers

Domain experts

Machines

Ontologists

slide6

Why build an anatomy ontology?

A simple example

Number of genes annotated to each of the following

brain parts in an ontology:

brain 20

part_of hindbrain 15

part_ofrhombomere10

Query brain without ontology 20

Query brain with ontology 45

Ontologies can facilitate grouping and retrieval of data

slide7

There are many useful ways to classify parts of organisms:

  • its parts and their arrangement
  • its relation to other structures

what is it: part of; connected to; adjacent to, overlapping?

  • its shape
  • its function
  • its developmental origins
  • its species or clade
  • its evolutionary history

Cajal 1915, “Accept the view that nothing in nature is useless, even from the human point of view.”

an ontology is a classification
An ontology is a classification

appendage

antenna

wing

fore

wing

hindwing

relationships record classifications too
Relationships record classifications too

‘leg’ SubClassOfpart_ofsome thoracic segment

part_ofsome ‘thoracic segment

leg

wing

slide10

Multiple inheritance is very hard to manage by hand

  • It is difficult to keep track of multiple
  • classification chains to:
  • ensure completeness;
  • avoid redundancy;
  • Incorrectinheritance of classification criteria from a distant superclass
slide11

The knowledge in an ontology can make the reasons for classification explicit

Any sense organ that functions in the detection of smell is an olfactory sense organ

capable_ofsome detection of smell

olfactory

sense

organ

sense organ

slide12

Classifying

capable_ofsome

detection of smell

sense organ

nose

nose

olfactory

sense

organ

capable_ofsome detection of smell

sense organ

nose

compositionality and avoiding asserted multiple inheritance
Compositionality and avoiding asserted multiple inheritance

Let the reasoner do the work!

  • We can logically define composed classes and create complex definitions from simpler ones
    • aka: building blocks, cross-products, logical definitions
  • Descriptions can be composed at any time
    • Ontology construction time (pre-composition)
    • Annotation time (post-composition)
  • Formal necessary and sufficient definitions + a reasoner
    • Automatic (and therefore manageable) classification
    • Requires subtype classification, so apart from the root term(s), no term should lack an is_a parent.
e xample of a post composed anatomical entity
Example of a post-composed anatomical entity

Plasma membrane of spermatocyte

  • Plasma membrane[GO CC]
  • Spermatocyte[Cell Ontology]

Genus

Differentia

a plasma membranewhich is part_of a spermatocyte

Gene Ontology

Basic Formal Ontology

Cell Ontology

many perspectives many ontologies
Many perspectives, many ontologies

behavior

gross

anatomy

clinical disorders

nervous system

processes

phenotypes

evolutionary

characters

development

physiological processes

neural crest

tissues

cells

cellular processes

cell

anatomy

proteins

reactions

chemical entities

what kinds of anatomy ontologies exist
What kinds of anatomy ontologies exist?

Species-centric and multi-species ontologies

Species neutral ontologies

Mouse

  • MA (adult)
  • EMAP / EMAPA (embryonic)

Human

  • FMA (adult)
  • EHDAA2 (CS1-CS20)

Amphibian

  • AAO
  • XAO

Fish

  • ZFA (zebrafish)
  • MFO (medaka)
  • TAO (teleosts)

Nematode

  • WBbt (c elegans)

Arthropod

  • FBbt (Drosophila)
  • TGMA (Mosquito)
  • HAO (hymenoptera)
  • Arthropod anatomy ontology

Plant ontology

CARO (common anatomy reference ontology)

Uberon (cross-species anatomy)

vHOG (vertebrate homologous organs)

CL (cell ontology)

GO (gene ontology)

Phenotype ontologies

MP mammalian phenotype

HP human phenotype

WB worm phenotype

species centric ontologies the z ebrafish anatomy ontology
Species-centric ontologiesThe Zebrafish Anatomy Ontology

Used to record gene expression and phenotypes at different stages of development

ontologies built for one species will not work for others
Ontologies built for one species will not work for others

http://ccm.ucdavis.edu/bcancercd/22/mouse_figure.html

http://fme.biostr.washington.edu:8080/FME/index.html

slide19

Multi-species anatomy ontologies

The Plant Ontology

Seed plants

(Angiosperms and Gymnosperms)

Pteridophytes

(Ferns and Lycopods)

Bryophytes

(Mosses, Hornworts and Liverworts)

Algae

Challenge is in representing diversity in anatomy, morphology, life cycles, growth patterns

Bowman et al, Cell, 2007

example of complexity arising from multiple species contexts
Example of complexity arising from multiple species-contexts

cell

nucleate cell

enucleate cell

not applicable in all contexts

erythrocyte

example of complexity arising from multiple species contexts1
Example of complexity arising from multiple species-contexts

cell

species ontologies

attached at appropriate

level

nucleate cell

enucleate cell

CL:0000232

erythrocyte

CL:0000592

CL:0000562

nucleate erythrocyte

enucleate erythrocyte

zebrafish nucleate erythrocyte

human erythrocyte

FMA:81100

ZFA:0009256

slide22

Using reasoners to detect errors

only_in_taxon

UBERON: bone

Vertebrata

disjoint with

is_a

is_a

Drosophila melanogaster

Homo sapiens

UBERON: tibia

is_a

is_a

part_of

part_of

Fruit fly FBbt ‘tibia’

Human FMA ‘tibia’

Developmental Biology, Scott Gilbert, 6th ed.

slide23

The Gene Ontology has an anatomy ontology

zebrafish

Look ma, no pons!

human

slide24

Phenotype ontologies also have inherent anatomy

WBbt

C. elegans

phenotype

Designed primarily for annotation of phenotypes within a single species

slide25

Representingdifferent levels of granularity

GO

lateral line development

neuromast development

?

hair cell development

neuromast part_of lateral line

?

hair cell part_ofneuromast

cilium development

cilium part_ofhair cell part_ofneuromast

slide26

The problem:Data Silos

is_a (SubClassOf)

part_of

GO

develops_from

FMA

surrounded_by

multicellularorganismal process

EHDAA2

organ system

solid organ

pharyngeal region

respiratory gaseous exchange

respiratory primordium

respiratory system

parenchymatous organ

lung bud

respiratory system process

lung

MA

Lower respiratory tract

lobular organ

thoracic cavity

organ system

MPO

abnormal respiratory system morphology

thoracic cavity organ

respiratory system

pleural sac

lung

abnormal lung morphology

lung

abnormal pulmonary acinus morphology

pulmonary acinus

abnormal pulmonary alveolus morphology

alveolar sac

lung

alveolus

slide27

How to synchronize anatomy ontologies

Three approaches:

  • Mapping
  • Direct reconciliation
  • Synchronization using imports/MIREOT
zebrafish terms are is a subtypes of teleost terms
Zebrafish terms are is_asubtypes of teleost terms

Reconciliation and linking between TAO and ZFA

Teleost Anatomy Ontology

Zebrafish Anatomy

is_a

Logic implemented via Xrefs- difficult to keep synchronized

slide30

The Common Anatomy Reference Ontology

CARO is a structural classification based on granularity

From the bottom up:

Cell component

Cell

Portion of tissue

Multi-tissue structure

From the top down:

Organism subdivision

Anatomical system

Acellular structures

Note: CARO is being updated to be more interoperable, include logical definitions, and functional differentia

slide31

Synchronization by import across ontologies

CARO

VAO

Present TAO

Modularized ontology

One can import a whole ontology or just portions of another ontology

MIREOT: Minimum information to reference an external ontology term

slide33

Uberon classes generalize species-specific ones, and connect to other ontologies via a variety of relations

is_a (SubClassOf)

anatomical structure

part_of

develops_from

capable_of

endoderm

is_a (taxon equivalent)

only_in_taxon

organ part

foregut

swim bladder

organ

endoderm of forgut

NCBITaxon:

Actinopterygii

respiration organ

respiratory primordium

GO: respiratory gaseous exchange

pulmonary acinus

alveolus

lung

lung primordium

NCBITaxon: Mammalia

alveolus of lung

alveolar sac

lung bud

FMA: pulmonary alveolus

FMA:lung

MA:lung alveolus

MA:lung

EHDAA:

lung bud

slide34

OntoFox: a Web Server for MIREOTing

  • Good things:
  • Based on MIREOT principle
  • Web-based data input and output
  • Output OWL file can be directly imported in your ontology
  • No programming needed
  • Programmatically accessible
  • Improvements:
  • Integration into ontology editing tools
  • More customizable

http://ontofox.hegroup.org

proposed model moving forward
Proposed model moving forward
  • Maintain series of ontologies at different taxonomic levels

- euk, plant, metazoan, vertebrate, mollusc, arthropod, insect, mammal, human, drosophila

  • Each ontology imports/MIREOTs relevant subset of ontology “above” it

- this is recursive

  • Subtypes are only introduced as needed
  • Work together on commonalities at appropriate level above your ontology
leveraging an integrated set of ontologies
Leveraging an integrated set of ontologies

cross-ontology

link (sample)

caro /uberon/all

cell

tissue

import

metazoa

skeleton

nervous system

gut

gonad

appendage

circulatory system

gland

mesoderm

respiratory

airway

larva

muscle

tissue

skeletal

tissue

mollusca

arthropoda

vertebrata

trachea

bone

mantle

mushroom body

limb

fin

vertebra

tibia

shell

cuticle

vertebral

column

foot

antenna

mesonephros

parietal

bone

cephalopod

drosophila

teleost

mammalia

amphibia

tentacle

neuron types XYZ

weberianossicle

mammary gland

tibiafibula

brachial lobe

mouse

human

zebrafish

NO pons

not all classification is useful
Not all classification is useful

About thirty years ago there was much talk that geologists ought only to observe and not theorise; and I well remember some one saying that at this rate a man might as well go into a gravel-pit and count the pebbles and describe the colours.

C. Darwin

Be practical: Build ontologies for what you need and for what can be reused

semantic similarity of phenotypes
Semantic Similarity of Phenotypes

MP

ZFA+PATO

FBbt+PATO

FMA+PATO

"Linking Human Diseases to Animal Models Using Ontology-Based Phenotype Annotation." PLoSBiol 7(11): e1000247. doi:10.1371/journal.pbio.1000247 Washington NL, Haendel MA, Mungall CJ, Ashburner M, Westerfield M, Lewis SE

slide40

Querying for genes in similar structures across species

polychaeteparapodia

ascidian ampulla

A

B

Vertebrata

tetrapod limbs

Ascidians

ampullae

Echinodermata

tube feet

sea urchin tube feet

mouse limb

Arthropoda

C

D

E

Annelida

parapodia

Mollusca

Distal-less orthologs participate in distal-proximal pattern formation and appendage morphogenesis

Panganibanet al., PNAS, 1997

slide41

Anatomy ontologies in 2012

  • Identify key points of integration between ontologies
  • Modularize based on domain or taxon
  • Import and reuse rather than cross-referencing or “aligning”
  • Let the reasoner help do the work
  • Work together to distribute work

Reproduced with permission, Jason Freeny

http://web.mac.com/moistproduction/flash/index.html

what is evidence
What is evidence?

ECO:000000X

Imaging assay evidence

Synaptolaemuscingulatus

AMNH 91095

Phenotype (character) annotation:

S. Cingulatus: mesethmoid

narrow

OBI:Specimen

Drawing about anatomical entity

OBI:Conclusion

(textual entity)

OBI:Image

material_processing

is_output

is_output

is_input

Draw prepared specimen

OBI:imaging assay

Brian, 2008, maybe in Venezuela

cleared and stained for

cartilage and bone

OBI: Interpreting Data-

phenotypic assessment

is_input

OBI:processed specimen

Sidlauskas and Vari, Zoological Journal of the Linnean Society, 2008, 154, 70–210

anatomical evidence is cumulative and synergistic
Anatomical evidence is cumulative and synergistic

ECO:0000080

phylogenetic evidence

Synaptolaemuscingulatus

AMNH 91095

mesethmoid

narrow

ECO:0000071

morphological similarity evidence

Caenotropusmaculosus

USNM 231545

mesethmoid

narrow

.

is_input

is_output

Schizodonfasciatus

INPA 21606

mesethmoid

wide

.

phylogeny

Brian, 2008

.

OBI:Conclusion

.

Phylogeny construction using PAUP* 4.0 Beta 10

OBI: Interpreting Data

the means to the end matters
The means to the end matters

ECO:0000080

phylogenetic evidence

Synaptolaemuscingulatus

AMNH 91095

Mesethmoid

ECO:0000071

sequence similarity evidence

Caenotropusmaculosus

USNM 231545

mesethmoid

narrow

.

is_input

is_output

Schizodonfasciatus

INPA 21606

mesethmoid

wide

.

phylogeny

Brian, 2008

.

OBI:Conclusion

.

Phylogeny construction using PAUP* 4.0 Beta 10

OBI: Interpreting Data

so what should one do about evidence
So what should one do about evidence?
  • Keep in mind that as you record your phenotype data, the means by which you obtained it can matter later one
  • Others may want to use your data, and they too will care
  • You may find that how you know what you know depends on the means to the end
  • You can work with ECO and OBI to get the terms you need for your work
acknowledgments
Acknowledgments
  • Jonathan Bard
  • Marcus Chibucos
  • WasilaDahdul
  • Paula Mabee
  • Chris Mungall
  • David Osumi-Sutherland
  • Alan Ruttenberg
  • Erik Segerdell
  • Carlo Torniai
  • Matt Yoder
  • JieZheng
  • AND numerous others

Larson, October 1987