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TopoICSim: a new semantic similarity measure based on gene ontology.

ABSTRACT: The 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.Here 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.The 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 .

SUBMITTER: Ehsani R

PROVIDER: S-EPMC4966780 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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TopoICSim: a new semantic similarity measure based on gene ontology.

Ehsani Rezvan R Drabløs Finn F

BMC bioinformatics 20160729 1

<h4>Background</h4>The 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 ...[more]

PMID: 27473391

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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.

Project description:BackgroundThe Gene Ontology (GO) is a well known controlled vocabulary describing the biological process, molecular function and cellular component aspects of gene annotation. It has become a widely used knowledge source in bioinformatics for annotating genes and measuring their semantic similarity. These measures generally involve the GO graph structure, the information content of GO aspects, or a combination of both. However, only a few of the semantic similarity measures described so far can handle GO annotations differently according to their origin (i.e. their evidence codes).ResultsWe present here a new semantic similarity measure called IntelliGO which integrates several complementary properties in a novel vector space model. The coefficients associated with each GO term that annotates a given gene or protein include its information content as well as a customized value for each type of GO evidence code. The generalized cosine similarity measure, used for calculating the dot product between two vectors, has been rigorously adapted to the context of the GO graph. The IntelliGO similarity measure is tested on two benchmark datasets consisting of KEGG pathways and Pfam domains grouped as clans, considering the GO biological process and molecular function terms, respectively, for a total of 683 yeast and human genes and involving more than 67,900 pair-wise comparisons. The ability of the IntelliGO similarity measure to express the biological cohesion of sets of genes compares favourably to four existing similarity measures. For inter-set comparison, it consistently discriminates between distinct sets of genes. Furthermore, the IntelliGO similarity measure allows the influence of weights assigned to evidence codes to be checked. Finally, the results obtained with a complementary reference technique give intermediate but correct correlation values with the sequence similarity, Pfam, and Enzyme classifications when compared to previously published measures.ConclusionsThe IntelliGO similarity measure provides a customizable and comprehensive method for quantifying gene similarity based on GO annotations. It also displays a robust set-discriminating power which suggests it will be useful for functional clustering.AvailabilityAn on-line version of the IntelliGO similarity measure is available at: http://bioinfo.loria.fr/Members/benabdsi/intelligo_project/

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TopoICSim: a new semantic similarity measure based on gene ontology.

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TopoICSim: a new semantic similarity measure based on gene ontology.

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