Ontology based analyses methods ++

• develop a grammar for making productions using mf, bp, cl: – derive a higher level grammar for next level of

productions derive a formal annotation language?

• Add structure awareness: Create an iconic mapping for cl terms to facilitate novel analyses.

• Add time awareness: express the temporal dimension and have time-dependent annotations

GO based analysis of microarray data

TF-binding site & Annotation data

TF-sites show that the ABRE and GBF sites are enriched in these genes.

Component and function annotations show that these genes are located in the chloroplast thylakoid membrane, are part of the light-harvesting complex and have the molecular function of chlorophyll binding and electron transport.

Clench is useful … but we need more!

• Clench helps the biologist interpret a list of genes and form a result statement such as:

– The photosynthesis genes located in the chloroplast are repressed in response to ozone stress and have the ABRE binding site enriched in their promoters.

• More at www.personal.psu.edu/nhs109/Clench

Within-ontology “grammars”

OBOL

Relations Ontology

Between-ontology “grammars”

OBOL

Relations Ontology

OBOL

Relations Ontology

?<link>?<Some MF> in

<Some BP>

Payoff: If we have between-ontology grammars

• We can systematically store the interpretations (or results) of GO based analyses

• We can browse [gene-expression] data in [particular ontology] centric views– Work of Gennari et al

• We can create semantically rich annotations that span multiple ontologies.

Storing GO based analysis reports

The photosynthesis genes located in the chloroplast are repressed in response to ozone stress and have the ABRE binding site enriched in their promoters.

The genes of the photosynthesis proteins located in the chloroplast show a decrease in their mRNA level in response to ozone stress and have the ABRE binding site enriched in their promoters.

Anatomy centric views by Gennari et al

• Established links between the cellular structure terms in FMA and the GO cellular component terms– Did it for 150 terms

• Established links between tissue-region annotations and brain anatomy terms in FMA

Cyclin D1 is associated with cellular proliferation in colon

Cyclin D1 is associated with neuronal degeneration in brain

Cyclin D1 has <mf> in cellular proliferation in colon

Semantically rich annotations

1. Relationship ontology 2. Mouse Pathology ontology 3. Tissue/Organ 4. Gene ontology

mRNA of genes encoding proteins with mf in bp at cc is increased in sample-id which shows some pathology in some tissue in some organ

Basal layer of organ shows membranous staining

Queries enabled: 1. Identify all images with a specific pathology 2. Identify cases with pathology and some gene expression changes 3. Correlate changes biological processes with change in morphology

Discovery enabled: 1. Classify samples in expression space and “look” for histological changes that

correlate with it.

WHY

HOW

Ontology based analyses methods ++

• develop a grammar for making productions using mf, bp, cl: – derive a higher level grammar for next level of

productions derive a formal Annotation language?

• Add structure awareness: Create an iconic mapping for cl terms to facilitate novel analyses.

• Add time awareness: express the temporal dimension and have time-dependent annotations

What about 3D structure of the cell?

Payoff: If we have iconic mappings

• We can browse ontologies in an anatomy centered manner

• Can use these new views for facilitating the annotation process– i.e. improve curator annotation tool interaction

• Create novel visualizations for interpreting high dimensional datasets.– Time course data [coming few slides later]

– Integrating gene expression, protein expression and metabolomic datasets.

Ontology based analyses methods ++

• develop a grammar for making productions using mf, bp, cl: – derive a higher level grammar for next level of

productions derive a formal Annotation language?

• Add structure awareness: Create an iconic mapping for cl terms to facilitate novel analyses.

• Add time awareness: express the temporal dimension and have time-dependent annotations

What about the temporal dimension?

Overlay time course Overlay time course data onto the GO tree.data onto the GO tree.

See how the See how the ‘enriched’ categories ‘enriched’ categories change over time.change over time.

Understand the Understand the dynamics of the dynamics of the biological biological phenomenon being phenomenon being studied.studied.

– Will complement Will complement pathway based pathway based analysis analysis approachesapproaches

How about cell structure and time?