Dataset Information

Gene Ontology term overlap as a measure of gene functional similarity.

ABSTRACT:

Background

The availability of various high-throughput experimental and computational methods allows biologists to rapidly infer functional relationships between genes. It is often necessary to evaluate these predictions computationally, a task that requires a reference database for functional relatedness. One such reference is the Gene Ontology (GO). A number of groups have suggested that the semantic similarity of the GO annotations of genes can serve as a proxy for functional relatedness. Here we evaluate a simple measure of semantic similarity, term overlap (TO).

Results

We computed the TO for randomly selected gene pairs from the mouse genome. For comparison, we implemented six previously reported semantic similarity measures that share the feature of using computation of probabilities of terms to infer information content, in addition to three vector based approaches and a normalized version of the TO measure. We find that the overlap measure is highly correlated with the others but differs in detail. TO is at least as good a predictor of sequence similarity as the other measures. We further show that term overlap may avoid some problems that affect the probability-based measures. Term overlap is also much faster to compute than the information content-based measures.

Conclusion

Our experiments suggest that term overlap can serve as a simple and fast alternative to other approaches which use explicit information content estimation or require complex pre-calculations, while also avoiding problems that some other measures may encounter.

SUBMITTER: Mistry M

PROVIDER: S-EPMC2518162 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature

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Publications

Gene Ontology term overlap as a measure of gene functional similarity.

Mistry Meeta M Pavlidis Paul P

BMC bioinformatics 20080804

<h4>Background</h4>The availability of various high-throughput experimental and computational methods allows biologists to rapidly infer functional relationships between genes. It is often necessary to evaluate these predictions computationally, a task that requires a reference database for functional relatedness. One such reference is the Gene Ontology (GO). A number of groups have suggested that the semantic similarity of the GO annotations of genes can serve as a proxy for functional relatedn ...[more]

PMID: 18680592

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Project description:BackgroundThe Gene Ontology (GO) is a dynamic, controlled vocabulary that describes the cellular function of genes and proteins according to tree major categories: biological process, molecular function and cellular component. It has become widely used in many bioinformatics applications for annotating genes and measuring their semantic similarity, rather than their sequence similarity. Generally speaking, semantic similarity measures involve the GO tree topology, information content of GO terms, or a combination of both.ResultsHere we present a new semantic similarity measure called TopoICSim (Topological Information Content Similarity) which uses information on the specific paths between GO terms based on the topology of the GO tree, and the distribution of information content along these paths. The TopoICSim algorithm was evaluated on two human benchmark datasets based on KEGG pathways and Pfam domains grouped as clans, using GO terms from either the biological process or molecular function. The performance of the TopoICSim measure compared favorably to five existing methods. Furthermore, the TopoICSim similarity was also tested on gene/protein sets defined by correlated gene expression, using three human datasets, and showed improved performance compared to two previously published similarity measures. Finally we used an online benchmarking resource which evaluates any similarity measure against a set of 11 similarity measures in three tests, using gene/protein sets based on sequence similarity, Pfam domains, and enzyme classifications. The results for TopoICSim showed improved performance relative to most of the measures included in the benchmarking, and in particular a very robust performance throughout the different tests.ConclusionsThe TopoICSim similarity measure provides a competitive method with robust performance for quantification of semantic similarity between genes and proteins based on GO annotations. An R script for TopoICSim is available at http://bigr.medisin.ntnu.no/tools/TopoICSim.R .

Project description:BackgroundVarious measures of semantic similarity of terms in bio-ontologies such as the Gene Ontology (GO) have been used to compare gene products. Such measures of similarity have been used to annotate uncharacterized gene products and group gene products into functional groups. There are various ways to measure semantic similarity, either using the topological structure of the ontology, the instances (gene products) associated with terms or a mixture of both. We focus on an instance level definition of semantic similarity while using the information contained in the ontology, both in the graphical structure of the ontology and the semantics of relations between terms, to provide constraints on our instance level description.Semantic similarity of terms is extended to annotations by various approaches, either though aggregation operations such as min, max and average or through an extrapolative method. These approaches introduce assumptions about how semantic similarity of terms relates to the semantic similarity of annotations that do not necessarily reflect how terms relate to each other.ResultsWe exploit the semantics of relations in the GO to construct an algorithm called SSA that provides the basis of a framework that naturally extends instance based methods of semantic similarity of terms, such as Resnik's measure, to describing annotations and not just terms. Our measure attempts to correctly interpret how terms combine via their relationships in the ontological hierarchy. SSA uses these relationships to identify the most specific common ancestors between terms. We outline the set of cases in which terms can combine and associate partial order constraints with each case that order the specificity of terms. These cases form the basis for the SSA algorithm. The set of associated constraints also provide a set of principles that any improvement on our method should seek to satisfy.ConclusionWe derive a measure of semantic similarity between annotations that exploits all available information without introducing assumptions about the nature of the ontology or data. We preserve the principles underlying instance based methods of semantic similarity of terms at the annotation level. As a result our measure better describes the information contained in annotations associated with gene products and as a result is better suited to characterizing and classifying gene products through their annotations.

Dataset Information

Gene Ontology term overlap as a measure of gene functional similarity.

Background

Results

Conclusion

Publications

Gene Ontology term overlap as a measure of gene functional similarity.

Similar Datasets

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