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.

Contents

1. DO Annotation
   1. Basic parts of a DO Annotation
   2. Optional additional parts of a DO Annotation
   3. Annotation Methods
      • Manually curated
      • High-throughput
      • Computational
2. Searching and Accessing DO Terms/Annotations in SGD
   1. Locus Summary Page
   2. DO Annotations Page
   3. DO Term Page

DO Annotation

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:

These aspects of a DO annotation are all displayed on SGD's DO Evidence and References pages; see, for example, this one for the CCC2 DO Annotations.

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.

Annotation Methods

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.

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.

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: