Jim Hu's presentation at the Biocurator 2012 conference: Developing an Ontology for Microbial Phenotypes

1. Developing an Ontology for Microbial
Phenotypes
#41
Jim Hu

2. "Before the physical basis of genes was
understood, associating phenotypes with a heritable
unit laid the foundation of modern genetics" - Nichols
et al 2011

3. Goals
• Build a classification system (ontology) for microbial
phenotypes
• Build an annotation system and annotate microbial
phenotypes
– Given a phenotype, identify kinds of genes and functions
likely to be involved
– Given a gene, identify phenotypes that may aid
understanding of function
– Correlate phenotypes to each other
– Connect genotypes and phenotypes
• Not there yet!

4. What’s a phenotype?
• Observable characteristics
• Individual
• Genotype
• Environment
http://www.flickr.com/photos/max_westby/54275159/

5. Building OMP
(Ontology of Microbial Phenotypes)
Expertise
Literature
Annotation
Examples Ontology system
Draft
annotations

6. Building OMP
(Ontology of Microbial Phenotypes)
Expertise
Literature
Annotation
Examples Ontology system
Draft
annotations

7. Entities and Qualities
• Existing phenotype ontologies are based on the
PATO entity-quality system
– Entity: a trait, object, process
– Quality: a property of an entity
– Example from mouse phenotype ontology:

8. Entities and Qualities
• Making this work for microbes
– In some cases the entities are analogous to anatomy terms
for microbial cells

9. Entities and Qualities
• Making this work for microbes
– Other cases are population behaviors
Budrene and Berg (1991) Nature 349:630 Courtesy of Bonnie Bassler

10. State vs Relative Phenotypes
• Characteristics of a species/type strain
• Changes relative to a reference strain
– Not necessarily relative to wild-type

11. What do we mean by observable?
• Observations vs. inferences
– Lac-
• Where do we draw the line?
– Loss of enzyme activity in an extract: yes
– Altered folding of a purified protein: no
– Expression patterns of specific genes: yes?
– Specific transcriptome patterns: no

12. Building OMP
(Ontology of Microbial Phenotypes)
Expertise
Literature
Annotation
Examples Ontology system
Draft
annotations

13. What is the object of annotation?
• Individuals/populations?
• Genes?
• Genotypes?
– “relevant genotypes”?
– Genotype differences?

14. Things the annotation system needs to
express
• Properties of wt type strains:
– 1. E. coli wt has_phenotype lactose utilization
• Mutant phenotypes
– 2. E. coli cya has_phenotype decreased lactose utilization
• relative_to 1
• Environmental dependence
– 3. E. coli cya has_phenotype increased lactose utilization in
Environment: + cAMP
• relative_to 2
• Genetic interaction
– 3. E. coli cya, crp* has_phenotype increased lactose
utilization
• relative_to 2

15. Components needed
• Unique annotation ID
• Accessions for genotypes for all species/strains
– Genes and alleles in a pangenome context
• OMP
• Relationships for relative phenotypes
• Environments
• ECO for evidence
• Reference

16. Future
• Build the needed components
– OMP in progress
– ECO in progress
– Universal genotype database?!
– Environment ontology?
• Build infrastructure
– OMP wiki: http://microbialphenotypes.org
– Sourceforge SVN for OMP
• Coordination with other phenotype projects
• Example annotation set for E. coli

17. Acknowledgements etc.
• TAMU
– Debby Siegele
– Adrienne Zweifel • NIH R01 GM089636
– Jon Herrera
– Will Meza • http://microbialphenotypes.org
– Whitley Lanier • micropheno
• IGS/Maryland
– Michelle Gwinn Giglio
– Marcus Chibucos
• Virginia Commonwealth
– Peter Uetz
– Kelly O'Briant
– Matt Feltz
– Robel Hailu Wolde