APPLYING BREED AND PHENE ONTOLOGIES TO REPORTING AND ANALYSIS OF INHERITED CONDITIONS IN ANIMALS

Imke Tammen and Frank W. Nicholas

Sydney School of Veterinary Science

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Image created by Bozena Jantulek

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Outline

• Background
• Reporting & analysis of inherited diseases at USYD
• Online Mendelian Inheritance in Animals (OMIA)
• Anstee Hub for Inherited Diseases in Animals (AHIDA) (under development)
• Molecular characterisation of inherited conditions in animals (not included)
• Why we need ontologies in OMIA / AHIDA
• What we have done so far
• Conclusions

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Background: Inherited diseases

Humans

• ~10,000 (WHO) / ~6000 (OMIM) monogenic diseases
• We are all carriers of multiple deleterious recessive alleles�

Animals

• Impact on welfare / productivity
• Often misdiagnosed and/or underreported
• Negative stakeholder perceptions
• Risk of affected animals being born can be reduced once mode of inheritance and/or causal variants have been identified

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Online Mendelian Inheritance in Animals https://omia.org/home/

OMIA is a freely available, comprehensive annotated online catalogue of inherited disorders and traits (phenes) in animals

• Online since 26^th May 1995 (27^th birthday is coming up ☺)
• > 2200 phenes in > 300 species
• > 4100 phene-species
• > 28000 references

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OMIA ID (phene ID + species ID)

Reciprocal OMIM hyperlink to gene or trait entries

Information added by curators

OMIA: phene-species entry

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VARIANT TABLE

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Includes a unique OMIA variant ID, information about genomic, coding and protein coordinates in HGVS format and if available European Variation Archive (EVA) rs ID

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Downloadable for

• phene-species specific variants
• species specific variants
• all OMIA variants

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References - Pubmed/DOI hyperlinked

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Need for further initiatives

• Incidence of inherited disease is not readily available
• Globally animal owners and veterinarians often do not know who to contact for reporting / genetic counselling (Reporting platforms exist in Denmark and Ireland for cattle and in France for cattle and horses)
• DNA diagnostics can only be developed if researchers have access to reports of emerging inherited conditions
• Sydney School of Veterinary Science
• Ronald Anstee bequest: Anstee Hub for Inherited Diseases in Animals (AHIDA) for reporting and surveillance of inherited diseases in animals in Australia
• expected to go live: end of 2022

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Anstee Hub for Inherited Diseases in Animals (AHIDA)

Veterinarians and animal owners

• submit information about suspected inherited diseases
• will be linked to information about previously described diseases
• will be directed to information about possible DNA diagnostics (if they exist)
• can be connected to research teams (on request)

Collaborating researchers

• can nominate an interest for a species/breed or specific type of condition

Genotyping providers

• can provide information about the DNA diagnostics offered
• can provide information about frequencies of disease variants

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Need for ontologies in AHIDA and OMIA

• Computational representation of knowledge, using both human readable and machine-readable definitions for breeds, clinical signs, pathological finding and diagnosed diseases is needed
• Semantic-based integrative data analysis
• using reported clinical signs and pathological findings to assist with creation of differential diagnosis of underlying disease (including comparative approach)
• link to existing information
• link to research teams
• link to available DNA diagnostics

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Research

Diagnostics

Incidence reports to breed societies, public

Information about inherited conditions, available diagnostics or link to research teams

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What we have we done so far … in OMIA

1. Vertebrate breed ontology (VBO) (details presented by Sabrina Toro, available at https://monarch-initiative.github.io/vertebrate-breed-ontology/)
• created in collaboration with Monarch Initiative team, Iowa State University (ISU) and FAO
• inspired by ISU’s Livestock Breed Ontology
• using the FAO DAD-IS breed list as a basis.
• OMIA breeds are mapped to VBO

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What have we done so far … in OMIA

2. Introducing phene & disease ontologies to OMIA
1. Mammalian Phene Ontology (MPO) ‘major biological system headers’ have replaced existing OMIA ‘categories’ in advanced searches and the OMIA browse page to allow for searches based on organ or body systems: 1324/2233 OMIA phenes (59%)
2. Reciprocal OMIA - OMIM hyperlinks reviewed: 1086/2233 OMIA phenes have at least 1 OMIM link (49%)
3. Mapping of OMIA phenes to Upheno and HPO has commenced: 250 OMIA phenes mapped so far

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What have we done so far … in OMIA

3. Standardised variant information in variant tables
• ‘OMIA variant IDs’ added to variant tables (to be used as cross-platform unique unchanging variant IDs)
• Variant information downloadable in HGVS and VCF format
• Genomic positions updated to recent reference genomes
• Variant information submitted to create EVA rs IDs
• Working with genome browser providers to add ‘OMIA variant track’

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What have we done so far … AHIDA

AHIDA submission form development

• Submission forms for reporting of disease or nomination of research interest will include VBO, Upheno2 and Mondo look up for submission of information about breed, clinical and pathological signs and disease
• Submission forms for genotyping results are likely to be reported based on OMIA phene ID (in the future mapped to phene and disease ontologies) and OMIA variant ID (linked incompletely to EVA)

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Key challenges

• Getting familiar with ontology terminology & methods
• Mapping of ‘non-disease’ traits
• Integration with existing animalgenome.org ontologies (Vertebrate Trait Ontology and Clinical Measurement Ontology) needs to be considered
• Avian traits not included in Upheno2

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Summary

• OMIA could become the global repository for standardised and computable variant, breed and phene information on inherited diseases in animals with hyperlinks to other resources
• VBO will be available independent from OMIA
• AHIDA 1st across-species reporting and surveillance platform for inherited diseases with suspected mendelian mode of inheritance
• Use of ontologies is a unique opportunity for cross species analysis of health data across different species

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Acknowledgements�

OMIA - https://omia.org/acknowledgements/�AHIDA - Imke Tammen, Claire Wade, Frank Nicholas, Bianca Waud, Marina Gimeno, Brandon Velie (USYD) & Brendon O'Rourke (EMAI-DPI)

SIH - Marius Mather�Monarch Team - Sabrina Toro, Nicolas Matentzoglu, Nicole Vasilevsky, Christopher J Mungall, Melissa A Haendel

ISU - Zhi-Liang Hu, Cari Park and Jim Reecy�FAO - Gregoire Leroy and Roswitha Baumung

AHIDA is funded by a bequest to the University under the Will of the late Ronald Bruce Anstee and OMIA and AHIDA are supported by the Sydney Informatics Hub, a Core Research Facility of the University of Sydney

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