The Medical Action Ontology: A tool for annotating and analyzing treatments and clinical management of human disease.

BACKGROUND: Navigating the clinical literature to determine the optimal clinical management for rare diseases presents significant challenges. We introduce the Medical Action Ontology (MAxO), an ontology specifically designed to organize medical procedures, therapies, and interventions. METHODS: MAxO incorporates logical structures that link MAxO terms to numerous other ontologies within the OBO Foundry. Term development involves a blend of manual and semi-automated processes. Additionally, we have generated annotations detailing diagnostic modalities for specific phenotypic abnormalities defined by the Human Phenotype Ontology (HPO). We introduce a web application, POET, that facilitates MAxO annotations for specific medical actions for diseases using the Mondo Disease Ontology. FINDINGS: MAxO encompasses 1,757 terms spanning a wide range of biomedical domains, from human anatomy and investigations to the chemical and protein entities involved in biological processes. These terms annotate phenotypic features associated with specific disease (using HPO and Mondo). Presently, there are over 16,000 MAxO diagnostic annotations that target HPO terms. Through POET, we have created 413 MAxO annotations specifying treatments for 189 rare diseases. CONCLUSIONS: MAxO offers a computational representation of treatments and other actions taken for the clinical management of patients. Its development is closely coupled to Mondo and HPO, broadening the scope of our computational modeling of diseases and phenotypic features. We invite the community to contribute disease annotations using POET (https://poet.jax.org/). MAxO is available under the open-source CC-BY 4.0 license (https://github.com/monarch-initiative/MAxO). FUNDING: NHGRI 1U24HG011449-01A1 and NHGRI 5RM1HG010860-04.

The Medical Action Ontology: A Tool for Annotating and Analyzing Treatments and Clinical Management of Human Disease.

Navigating the vast landscape of clinical literature to find optimal treatments and management strategies can be a challenging task, especially for rare diseases. To address this task, we introduce the Medical Action Ontology (MAxO), the first ontology specifically designed to organize medical procedures, therapies, and interventions in a structured way. Currently, MAxO contains 1757 medical action terms added through a combination of manual and semi-automated processes. MAxO was developed with logical structures that make it compatible with several other ontologies within the Open Biological and Biomedical Ontologies (OBO) Foundry. These cover a wide range of biomedical domains, from human anatomy and investigations to the chemical and protein entities involved in biological processes. We have created a database of over 16000 annotations that describe diagnostic modalities for specific phenotypic abnormalities as defined by the Human Phenotype Ontology (HPO). Additionally, 413 annotations are provided for medical actions for 189 rare diseases. We have developed a web application called POET (https://poet.jax.org/) for the community to use to contribute MAxO annotations. MAxO provides a computational representation of treatments and other actions taken for the clinical management of patients. The development of MAxO is closely coupled to the Mondo Disease Ontology (Mondo) and the Human Phenotype Ontology (HPO) and expands the scope of our computational modeling of diseases and phenotypic features to include diagnostics and therapeutic actions. MAxO is available under the open-source CC-BY 4.0 license (https://github.com/monarch-initiative/MAxO).

Marginal ancestral contributions to atrial fibrillation in the Standardbred racehorse: Comparison of cases and controls.

Admissions of Standardbred racehorses (Std) to the Ontario Veterinary College Teaching Hospital (OVCTH) for treatment of atrial fibrillation (AF) began to increase in the early 1990s. The arrhythmia has been shown to have a modest heritability (h2 ≃ 0.15), with some stallions appearing as sires or sires of mares used in breeding (broodmares) of affected horses more frequently than others. The objective of this study was to determine the marginal genetic contributions of ancestors to cohorts of Std affected with AF and their contemporary control groups, and whether these ancestors contribute significantly more to the affected cohorts than to controls. All Std admitted to OVCTH for treatment of AF that were born between 1993 and 2007 comprised the affected case group (n = 168). Five randomly selected racing contemporaries for each Std admitted, assumed to not suffer from the arrhythmia, comprised the control group (n = 840). Three-year overlapping cohorts were created for case and control horses, determined according to year of birth, for a total of 26 cohorts. Marginal genetic contributions of ancestors to each cohort were determined and differences analyzed for statistical significance using a two-tailed paired t-test, with P ≤ 0.05 considered significant. The marginal contributions of 26 ancestors were significant, with 11 contributing significantly more to affected cohorts than the corresponding controls, and 15 contributing significantly more to controls than the corresponding affected cohorts. One stallion and one broodmare were very highly significant to affected cohorts at P ≤ 0.001, and nine stallions and three broodmares were very highly significant to control cohorts at P ≤ 0.001. Therefore, a number of stallions have statistically significant contributions to the genetics of Std affected with AF, while many others have statistically significant contributions to healthy Std. The arrhythmia appears to be particularly prevalent in the descendants of one sire family.

Breed predisposition and heritability of atrial fibrillation in the Standardbred horse: a retrospective case-control study.

OBJECTIVES: To assess evidence for genetic contributions to atrial fibrillation (AF) in the Standardbred horse. ANIMALS: Equine referrals to the Ontario Veterinary College Health Sciences Centre (OVCHSC) for 1985-2009, and age and gait matched breed registry controls. METHODS: Breeds presenting ≥ 5 times annually were tabulated (admission year and diagnosis; total 40,039; AF 396; no AF 39,643), and breed and year effects examined. Heritability and inbreeding coefficients were determined for Standardbred AF cases and racing contemporaries, and odds ratios for AF were calculated for frequently occurring sires. RESULTS: Year and breed effects on diagnosis were highly significant (Chi-Square 212.85, p < 0.0001, and 304.25, p < 0.0001, respectively). Year effect on diagnosis by breed was significant from 1997, and due to Standardbred admissions each year. Quarterhorses were significantly less likely to present with AF (OR 0.0578-0.6048), Standardbreds were more likely (OR 4.3874-10.9006). Heritability of AF on the underlying scale (h²(u)) was estimated at 29.6 ± 3.9% and on the observed binomial scale (h²(o)), at 9.6%. For horses born in 1994 or later, h²(u) was 31.1 ± 4.3% and h²(o), 10.1%. Of 22 first generation sires appearing ≥ 10 times in the case/control file, seven pacing and one trotting sire produced affected horses more frequently than expected (OR 2.66-66.32). Inbreeding was not a factor. CONCLUSIONS: There is genetic liability to AF in Standardbred horses, likely due to more than single genes with simple Mendelian inheritance. Genomic studies are required.