BIN-FUNC-Databases

Molecular Function Databases

 

Keywords:  EC numbers, GO, MSigDB, EcoCyc, KEGG

 

 

Caution!

This unit is under development. There is some contents here but it is incomplete and/or may change significantly: links may lead to nowhere, the contents is likely going to be rearranged, and objectives, deliverables etc. may be incomplete or missing. Do not work with this material until it is updated to "live" status.

 

Abstract

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This unit ...

Prerequisites

You need to complete the following units before beginning this one:

• BIN-Databases
• BIN-FUNC-Concepts

 

Objectives

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Outcomes

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Deliverables

• Time management: Before you begin, estimate how long it will take you to complete this unit. Then, record in your course journal: the number of hours you estimated, the number of hours you worked on the unit, and the amount of time that passed between start and completion of this unit.
• Journal: Document your progress in your course journal.
• Insights: If you find something particularly noteworthy about this unit, make a note in your insights! page.

 

Evaluation

Evaluation: NA

This unit is not evaluated for course marks.

 

Contents

Task:

• Read the introductory notes on databases that store gene function information.

EC

Enzyme Commission Codes ...

 

Further reading, links and resources

OBO Foundry (Open Biological and Biomedical Ontologies)

Sauro & Bergmann (2008) Standards and ontologies in computational systems biology. Essays Biochem 45:211-22. (pmid: 18793134)

[ PubMed ] [ DOI ] With the growing importance of computational models in systems biology there has been much interest in recent years to develop standard model interchange languages that permit biologists to easily exchange models between different software tools. In the present chapter two chief model exchange standards, SBML (Systems Biology Markup Language) and CellML are described. In addition, other related features including visual layout initiatives, ontologies and best practices for model annotation are discussed. Software tools such as developer libraries and basic editing tools are also introduced, together with a discussion on the future of modelling languages and visualization tools in systems biology.

Phenotype etc. Ontologies

Human Phenotype Ontology
See also:

Köhler et al. (2014) The Human Phenotype Ontology project: linking molecular biology and disease through phenotype data. Nucleic Acids Res 42:D966-74. (pmid: 24217912)

[ PubMed ] [ DOI ] The Human Phenotype Ontology (HPO) project, available at http://www.human-phenotype-ontology.org, provides a structured, comprehensive and well-defined set of 10,088 classes (terms) describing human phenotypic abnormalities and 13,326 subclass relations between the HPO classes. In addition we have developed logical definitions for 46% of all HPO classes using terms from ontologies for anatomy, cell types, function, embryology, pathology and other domains. This allows interoperability with several resources, especially those containing phenotype information on model organisms such as mouse and zebrafish. Here we describe the updated HPO database, which provides annotations of 7,278 human hereditary syndromes listed in OMIM, Orphanet and DECIPHER to classes of the HPO. Various meta-attributes such as frequency, references and negations are associated with each annotation. Several large-scale projects worldwide utilize the HPO for describing phenotype information in their datasets. We have therefore generated equivalence mappings to other phenotype vocabularies such as LDDB, Orphanet, MedDRA, UMLS and phenoDB, allowing integration of existing datasets and interoperability with multiple biomedical resources. We have created various ways to access the HPO database content using flat files, a MySQL database, and Web-based tools. All data and documentation on the HPO project can be found online.

Schriml et al. (2012) Disease Ontology: a backbone for disease semantic integration. Nucleic Acids Res 40:D940-6. (pmid: 22080554)

[ PubMed ] [ DOI ] The Disease Ontology (DO) database (http://disease-ontology.org) represents a comprehensive knowledge base of 8043 inherited, developmental and acquired human diseases (DO version 3, revision 2510). The DO web browser has been designed for speed, efficiency and robustness through the use of a graph database. Full-text contextual searching functionality using Lucene allows the querying of name, synonym, definition, DOID and cross-reference (xrefs) with complex Boolean search strings. The DO semantically integrates disease and medical vocabularies through extensive cross mapping and integration of MeSH, ICD, NCI's thesaurus, SNOMED CT and OMIM disease-specific terms and identifiers. The DO is utilized for disease annotation by major biomedical databases (e.g. Array Express, NIF, IEDB), as a standard representation of human disease in biomedical ontologies (e.g. IDO, Cell line ontology, NIFSTD ontology, Experimental Factor Ontology, Influenza Ontology), and as an ontological cross mappings resource between DO, MeSH and OMIM (e.g. GeneWiki). The DO project (http://diseaseontology.sf.net) has been incorporated into open source tools (e.g. Gene Answers, FunDO) to connect gene and disease biomedical data through the lens of human disease. The next iteration of the DO web browser will integrate DO's extended relations and logical definition representation along with these biomedical resource cross-mappings.

Evelo et al. (2011) Answering biological questions: querying a systems biology database for nutrigenomics. Genes Nutr 6:81-7. (pmid: 21437033)

[ PubMed ] [ DOI ] The requirement of systems biology for connecting different levels of biological research leads directly to a need for integrating vast amounts of diverse information in general and of omics data in particular. The nutritional phenotype database addresses this challenge for nutrigenomics. A particularly urgent objective in coping with the data avalanche is making biologically meaningful information accessible to the researcher. This contribution describes how we intend to meet this objective with the nutritional phenotype database. We outline relevant parts of the system architecture, describe the kinds of data managed by it, and show how the system can support retrieval of biologically meaningful information by means of ontologies, full-text queries, and structured queries. Our contribution points out critical points, describes several technical hurdles. It demonstrates how pathway analysis can improve queries and comparisons for nutrition studies. Finally, three directions for future research are given.

Oti et al. (2009) The biological coherence of human phenome databases. Am J Hum Genet 85:801-8. (pmid: 20004759)

[ PubMed ] [ DOI ] Disease networks are increasingly explored as a complement to networks centered around interactions between genes and proteins. The quality of disease networks is heavily dependent on the amount and quality of phenotype information in phenotype databases of human genetic diseases. We explored which aspects of phenotype database architecture and content best reflect the underlying biology of disease. We used the OMIM-based HPO, Orphanet, and POSSUM phenotype databases for this purpose and devised a biological coherence score based on the sharing of gene ontology annotation to investigate the degree to which phenotype similarity in these databases reflects related pathobiology. Our analyses support the notion that a fine-grained phenotype ontology enhances the accuracy of phenome representation. In addition, we find that the OMIM database that is most used by the human genetics community is heavily underannotated. We show that this problem can easily be overcome by simply adding data available in the POSSUM database to improve OMIM phenotype representations in the HPO. Also, we find that the use of feature frequency estimates--currently implemented only in the Orphanet database--significantly improves the quality of the phenome representation. Our data suggest that there is much to be gained by improving human phenome databases and that some of the measures needed to achieve this are relatively easy to implement. More generally, we propose that curation and more systematic annotation of human phenome databases can greatly improve the power of the phenotype for genetic disease analysis.

Groth et al. (2007) PhenomicDB: a new cross-species genotype/phenotype resource. Nucleic Acids Res 35:D696-9. (pmid: 16982638)

[ PubMed ] [ DOI ] Phenotypes are an important subject of biomedical research for which many repositories have already been created. Most of these databases are either dedicated to a single species or to a single disease of interest. With the advent of technologies to generate phenotypes in a high-throughput manner, not only is the volume of phenotype data growing fast but also the need to organize these data in more useful ways. We have created PhenomicDB (freely available at http://www.phenomicdb.de), a multi-species genotype/phenotype database, which shows phenotypes associated with their corresponding genes and grouped by gene orthologies across a variety of species. We have enhanced PhenomicDB recently by additionally incorporating quantitative and descriptive RNA interference (RNAi) screening data, by enabling the usage of phenotype ontology terms and by providing information on assays and cell lines. We envision that integration of classical phenotypes with high-throughput data will bring new momentum and insights to our understanding. Modern analysis tools under development may help exploiting this wealth of information to transform it into knowledge and, eventually, into novel therapeutic approaches.

 

Notes

 

Self-evaluation

 

 

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About ...
 
Author:

Boris Steipe <boris.steipe@utoronto.ca>

Created:

2017-08-05

Modified:

2017-08-05

Version:

0.1

Version history:

• 0.1 First stub

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