SGD Help: Disease Ontology (DO)
The Disease Ontology has been developed as a standardized ontology for human disease with the purpose of providing the biomedical community with consistent, reusable and sustainable descriptions of human disease terms, phenotype characteristics and related medical vocabulary disease concepts through collaborative efforts of researchers at Northwestern University, Center for Genetic Medicine and the University of Maryland School of Medicine, Institute for Genome Sciences. More information about DO can be found on their website: http://www.disease-ontology.org
Within SGD, DO annotations are used to describe human diseases that are associated with yeast homologs. DO annotations appear directly on the Locus Summary pages. More detail about the DO annotations or the DO terms are located on additional pages.
- DO Annotation
- Basic parts of a DO Annotation
- Optional additional parts of a DO Annotation
- Annotation Methods
- Manually curated
- Searching and Accessing DO Terms/Annotations in SGD
- Locus Summary Page
- DO Annotations Page
- DO Term Page
The DO is a resource for controlled vocabularies that integrate biomedical data associated with human disease. The open source DO project adapts terms from established medical terminologies. Similarly to the Gene Ontology (GO), DO combines controlled vocabulary of disease terms with a relational structure in its ontology.
The diagram to the right displays a subset of the Disease Ontology. As with GO, parent terms are structured with the is_a relationship above their child terms, which provide further specificity for the related disease terms.
Basic parts of a DO Annotation
A DO term, e.g., Menkes Disease, is associated with a gene, e.g., CCC2, to form a DO Annotation. In addition to the association between a gene and a DO term, a DO annotation must also be associated with a specific reference, an evidence code, and the date on which the annotation was made. Thus a basic DO annotation includes these pieces of information:
- Gene (or gene product)
- DO term
e.g., Menkes Disesae
The reference contains data or statements which support the annotation, or a description of the method by which the annotation was assigned.
- Evidence Code
The Evidence Code gives a basic indication of the type of data or statement that supports the annotation. DO annotations use the same set of evidence codes as used for GO Annotations. More information about the GO Evidence Codes is found in the Guide to GO Evidence Codes.
- Date on which the annotation was assigned or reviewed.
Optional additional parts of a DO Annotation
In addition to the basic, essential components of a DO annotation, some annotations have additional pieces of information when appropriate. This is specified by the With/From field:
For some evidence codes, it is useful to specify a second object that the gene being annotated interacted with or was compared to. For example, for Inferred from Genetic Interaction (IGI), it is useful to specify which other genes were involved in a genetic interaction with the gene being annotated. Similarly for Inferred from Physical Interaction (IPI), the "with field" specifies the gene products with which the gene product being annotated interacted. When used for Inferred from Sequence or Structural Similarity (ISS), the "with field" indicates what the gene being annotated was compared to in a sequence-based analysis.
To differentiate annotations made from published small scale experiments, genome-wide or high-throughput experiments and computational predictions, we have separated DO annotations at SGD into three sets:
- Manually curated DO annotations
Manually curated annotations are assigned by SGD curators inspecting the literature for each gene and forming annotations when a disease relationship to the DO is identified. When published literature is available, such annotations may include experimental evidence, sequence similarity, computational analyses, or on statements made by the authors.
- High-throughput DO Annotations
DO annotations from high-throughput experiments are assigned based on a variety of large scale methodologies, including genome-wide experiments. These DO annotations (or mappings to DO annotations) are generally sourced from authors, who often work in concert with SGD curators to incorporate information from these studies
- Computational DO Annotations
Computational DO annotations are generated within the Alliance of Genome Resources and imported to SGD. These annotations are made via homology relationships to genes in other model organisms.
At SGD, curators read the research literature and associate specific DO terms with the appropriate genes. We are regularly updating our DO annotations and encourage your feedback as knowledge of a gene's implication in human disease has improved since the most recent review date.
Accessing DO Annotations in SGD
Users can search for DO terms that match a text query, e.g. "atrophy", using the Search box located at the top right of SGD webpages. As you type your query potential DO terms are listed in a drop down list from the Search box, and clicking on an entry with the "Disease" designation will take you directly to the DO Term Page. Otherwise, entering text in the Search box results n a list of matches for your query.
Locus Summary Page
Every Locus Summary page contains a Disease section that lists DO terms, with associated evidence codes, that SGD curators have annotated to the gene of interest. From a gene's Locus Summary page, clicking on the Disease Details link takes you to the DO Annotations page for that gene, while clicking on a DO Term name will take you to the corresponding DO Term page. An example section for CCC2 is provided below:
DO Annotations Page
The DO Annotations page is accessible through the Disease tab at the top of the Locus Summary Page or via the Disease Details link within the associated summary section. It lists all the DO terms that have been used to annotate the particular gene, along with the specific reference(s) used to make each annotation and the evidence code(s) describing the type of evidence or statement found in that reference. Annotations are displayed in sortable tables separated by the three different annotation methods: Manually curated, high-throughput and computational DO Annotations.
The network diagram displays connections between different genes, in the form of DO terms they share. The diagram displays DO terms (orange circles) that are shared between the given gene (black circle), other yeast genes (blue circles), and human genes (green circles) based on the number of DO terms shared (slider at the bottom can be used to adjust this number). This diagram is also interactive, i.e. the gene names and DO terms are clickable from within the diagram and lead you to the respective Locus Summary Page or DO Term Pages.
DO Term Page
Clicking on a term name, from either the Disease section of the Locus Summary Page or within the DO Annotations Page for a particular gene, takes you to the DO Term Page for that term. The DO Term Page provides specific information about the DO term, listing a description and any synonyms or alternative phrases for the term name, its DOID number (a unique numerical identifier), and an ontology diagram view showing the relationship between this term and others in the ontology (similar to the first diagram of this help page).
Annotations of genes within SGD are summarized in a table, along with the relevant reference and evidence code for each annotation. More information on the DO term can be found by clicking on the DO ID link (e.g. DOID:12858). Additional annotations to this same term for genes in other model organisms, and human, can be accessed by clicking on the 'View DO Annotations for yeast and other model organisms at the Alliance of Genome Resources' link. An example of these links and annotation summary table is shown for Huntington's disease below: