Dataset Information

Improving the measurement of semantic similarity between gene ontology terms and gene products: insights from an edge- and IC-based hybrid method.

ABSTRACT:

Background

Explicit comparisons based on the semantic similarity of Gene Ontology terms provide a quantitative way to measure the functional similarity between gene products and are widely applied in large-scale genomic research via integration with other models. Previously, we presented an edge-based method, Relative Specificity Similarity (RSS), which takes the global position of relevant terms into account. However, edge-based semantic similarity metrics are sensitive to the intrinsic structure of GO and simply consider terms at the same level in the ontology to be equally specific nodes, revealing the weaknesses that could be complemented using information content (IC).

Results and conclusions

Here, we used the IC-based nodes to improve RSS and proposed a new method, Hybrid Relative Specificity Similarity (HRSS). HRSS outperformed other methods in distinguishing true protein-protein interactions from false. HRSS values were divided into four different levels of confidence for protein interactions. In addition, HRSS was statistically the best at obtaining the highest average functional similarity among human-mouse orthologs. Both HRSS and the groupwise measure, simGIC, are superior in correlation with sequence and Pfam similarities. Because different measures are best suited for different circumstances, we compared two pairwise strategies, the maximum and the best-match average, in the evaluation. The former was more effective at inferring physical protein-protein interactions, and the latter at estimating the functional conservation of orthologs and analyzing the CESSM datasets. In conclusion, HRSS can be applied to different biological problems by quantifying the functional similarity between gene products. The algorithm HRSS was implemented in the C programming language, which is freely available from http://cmb.bnu.edu.cn/hrss.

SUBMITTER: Wu X

PROVIDER: S-EPMC3669204 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Improving the measurement of semantic similarity between gene ontology terms and gene products: insights from an edge- and IC-based hybrid method.

Wu Xiaomei X Pang Erli E Lin Kui K Pei Zhen-Ming ZM

PloS one 20130531 5

<h4>Background</h4>Explicit comparisons based on the semantic similarity of Gene Ontology terms provide a quantitative way to measure the functional similarity between gene products and are widely applied in large-scale genomic research via integration with other models. Previously, we presented an edge-based method, Relative Specificity Similarity (RSS), which takes the global position of relevant terms into account. However, edge-based semantic similarity metrics are sensitive to the intrinsic ...[more]

PMID: 23741529

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Project description:BACKGROUND: With the development of high throughput methods of gene analyses, there is a growing need for mining tools to retrieve relevant articles in PubMed. As PubMed grows, literature searches become more complex and time-consuming. Automated search tools with good precision and recall are necessary. We developed GO2PUB to automatically enrich PubMed queries with gene names, symbols and synonyms annotated by a GO term of interest or one of its descendants. RESULTS: GO2PUB enriches PubMed queries based on selected GO terms and keywords. It processes the result and displays the PMID, title, authors, abstract and bibliographic references of the articles. Gene names, symbols and synonyms that have been generated as extra keywords from the GO terms are also highlighted. GO2PUB is based on a semantic expansion of PubMed queries using the semantic inheritance between terms through the GO graph. Two experts manually assessed the relevance of GO2PUB, GoPubMed and PubMed on three queries about lipid metabolism. Experts' agreement was high (kappa?=?0.88). GO2PUB returned 69% of the relevant articles, GoPubMed: 40% and PubMed: 29%. GO2PUB and GoPubMed have 17% of their results in common, corresponding to 24% of the total number of relevant results. 70% of the articles returned by more than one tool were relevant. 36% of the relevant articles were returned only by GO2PUB, 17% only by GoPubMed and 14% only by PubMed. For determining whether these results can be generalized, we generated twenty queries based on random GO terms with a granularity similar to those of the first three queries and compared the proportions of GO2PUB and GoPubMed results. These were respectively of 77% and 40% for the first queries, and of 70% and 38% for the random queries. The two experts also assessed the relevance of seven of the twenty queries (the three related to lipid metabolism and four related to other domains). Expert agreement was high (0.93 and 0.8). GO2PUB and GoPubMed performances were similar to those of the first queries. CONCLUSIONS: We demonstrated that the use of genes annotated by either GO terms of interest or a descendant of these GO terms yields some relevant articles ignored by other tools. The comparison of GO2PUB, based on semantic expansion, with GoPubMed, based on text mining techniques, showed that both tools are complementary. The analysis of the randomly-generated queries suggests that the results obtained about lipid metabolism can be generalized to other biological processes. GO2PUB is available at http://go2pub.genouest.org.

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

Improving the measurement of semantic similarity between gene ontology terms and gene products: insights from an edge- and IC-based hybrid method.

Background

Results and conclusions

Publications

Improving the measurement of semantic similarity between gene ontology terms and gene products: insights from an edge- and IC-based hybrid method.

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