Virulence Ontology

effort

Why we need a virulence ontology

• There is a lot of effort being expended to characterize pathogenic processes and systems

• However there is no comprehensive standardized system to capture this information in a way that allows one to easily compute on the data or to rapidly mine it.

• Therefore we need an ontology. (or as we will see a set of ontologies)

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Starting Materials

• TVFac (Toxin and Virulence Factors)– Los Alamos National Laboratory (LANL) – Chris Stubben, Murray Wolinsky

• Antibiotic Ontology– LANL– Jian Song, Murray Wolinsky

• Gemina/IDO (Infectious Disease Ontology)– Institute of Genome Sciences (IGS) U. Maryland– Lynn Schriml

• PAMGO/Pathema – IGS– Michelle Gwinn Giglio

• What are the core/shared terms between these ontologies?

(borrowed slide from MITRE presentation)

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Starting OntologiesBVF (Gemina) TVFac GO(PAMGO)

ToxinsDrug Resistance

GOPATO

Sequence OntologyTaxon IDs

CheBIMESH

(borrowed slide from MITRE presentation)

Aspects of Virulence

• Entering and living within a host– adhesion– entry into host– acquisition of nutrients from host– avoidance of host defenses– growth within host– modification of host morhphology or physiology– dissemination from host

• Toxin activity• Toxin biosynthesis• Antibiotic Resistance• Sequence Feature

SO

pathogenicity islandplasmidtransposable elementprophagencRNA

We need 3 new ontologies:

• Toxin associated processes and activities• Antibiotic Resistance• A Virulence Ontology to act as an umbrella that links

these (above) and the GO branches together and allows annotators to tag proteins as being “virulence factors”

Virulence Factor Ontology

• Virulence factor (root)– toxin associated processes– antibiotic resistance– adhesion– entry into host– acquisition of nutrients from host– avoidance of host defenses– growth within host– modification of host morhphology or physiology– dissemination from host

• This will be a very simple ontology - these terms will have no children. They will act as pointers to the more extensive other ontologies

How will we handle things already in GO?

• GO Slims• Separate slims for each major branch of the GO tree

which we need to describe virulence.• Slims will be “entry point” for people to drill down to

more specific terms if they have the desire and resources to do so.

Toxin Ontology

• toxin family– ADP ribosylating– pore-forming– etc.

• regulation of toxin gene expression• toxin biosynthesis• regulation of toxin biosynthesis• toxin accessory proteins

Antibiotic Resistance

• As a group, the virulence folks have not done much with antibiotic resistance

• There have been initial efforts on this by some people at LANL

• But while we were working on toxins, we discovered that Mihai Pop has been working on antibiotic resistance. His group has done extensive work on creating terms in this area, in collecting gene products, and in creating a web resource for searching and categorizing proteins.

• http://ardb.cbcb.umd.edu.

Wishes for a Web Resource

• We hope to create a web resource that organizes information around the umbrella virulence ontology.

• People will be able to search and view data from all of the contributing ontologies.

• It will have a web based annotation tool that points people to the correct sub-ontology for detailed annotations, while allowing broader annotations to the virulence ontology nodes - using a “checklist” aproach.

• It will provide a gold standard set of data for use in searching and automatic annotation.

Immediate Plans

• Firm up toxin ontology• Firm up umbrella virulence ontology• start pilot set of annotations on a subset of toxins (at

the same time we are firming up) to both make sure the ontologies are complete and to create a “gold standard” data set.

• Work with Mihai on antibiotic resistance