5,873 research outputs found

    IntelliGO: a new vector-based semantic similarity measure including annotation origin

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    International audienceThe 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). RESULTS: We 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. CONCLUSIONS: The 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. AVAILABILITY: An on-line version of the IntelliGO similarity measure is available at: http://bioinfo.loria.fr/Members/benabdsi/intelligo_project

    Inferring gene ontologies from pairwise similarity data.

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    MotivationWhile the manually curated Gene Ontology (GO) is widely used, inferring a GO directly from -omics data is a compelling new problem. Recognizing that ontologies are a directed acyclic graph (DAG) of terms and hierarchical relations, algorithms are needed that: analyze a full matrix of gene-gene pairwise similarities from -omics data; infer true hierarchical structure in these data rather than enforcing hierarchy as a computational artifact; and respect biological pleiotropy, by which a term in the hierarchy can relate to multiple higher level terms. Methods addressing these requirements are just beginning to emerge-none has been evaluated for GO inference.MethodsWe consider two algorithms [Clique Extracted Ontology (CliXO), LocalFitness] that uniquely satisfy these requirements, compared with methods including standard clustering. CliXO is a new approach that finds maximal cliques in a network induced by progressive thresholding of a similarity matrix. We evaluate each method's ability to reconstruct the GO biological process ontology from a similarity matrix based on (a) semantic similarities for GO itself or (b) three -omics datasets for yeast.ResultsFor task (a) using semantic similarity, CliXO accurately reconstructs GO (>99% precision, recall) and outperforms other approaches (<20% precision, <20% recall). For task (b) using -omics data, CliXO outperforms other methods using two -omics datasets and achieves ∼30% precision and recall using YeastNet v3, similar to an earlier approach (Network Extracted Ontology) and better than LocalFitness or standard clustering (20-25% precision, recall).ConclusionThis study provides algorithmic foundation for building gene ontologies by capturing hierarchical and pleiotropic structure embedded in biomolecular data

    Identification of disease-causing genes using microarray data mining and gene ontology

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    Background: One of the best and most accurate methods for identifying disease-causing genes is monitoring gene expression values in different samples using microarray technology. One of the shortcomings of microarray data is that they provide a small quantity of samples with respect to the number of genes. This problem reduces the classification accuracy of the methods, so gene selection is essential to improve the predictive accuracy and to identify potential marker genes for a disease. Among numerous existing methods for gene selection, support vector machine-based recursive feature elimination (SVMRFE) has become one of the leading methods, but its performance can be reduced because of the small sample size, noisy data and the fact that the method does not remove redundant genes. Methods: We propose a novel framework for gene selection which uses the advantageous features of conventional methods and addresses their weaknesses. In fact, we have combined the Fisher method and SVMRFE to utilize the advantages of a filtering method as well as an embedded method. Furthermore, we have added a redundancy reduction stage to address the weakness of the Fisher method and SVMRFE. In addition to gene expression values, the proposed method uses Gene Ontology which is a reliable source of information on genes. The use of Gene Ontology can compensate, in part, for the limitations of microarrays, such as having a small number of samples and erroneous measurement results. Results: The proposed method has been applied to colon, Diffuse Large B-Cell Lymphoma (DLBCL) and prostate cancer datasets. The empirical results show that our method has improved classification performance in terms of accuracy, sensitivity and specificity. In addition, the study of the molecular function of selected genes strengthened the hypothesis that these genes are involved in the process of cancer growth. Conclusions: The proposed method addresses the weakness of conventional methods by adding a redundancy reduction stage and utilizing Gene Ontology information. It predicts marker genes for colon, DLBCL and prostate cancer with a high accuracy. The predictions made in this study can serve as a list of candidates for subsequent wet-lab verification and might help in the search for a cure for cancers

    Ontology ranking based on the analysis of concept structures

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    In view of the need to provide tools to facilitate the reuse of existing knowledge structures such as ontologies, we present in this paper a system, AKTiveRank, for the ranking of ontologies. AKTiveRank uses as input the search terms provided by a knowledge engineer and, using the output of an ontology search engine, ranks the ontologies. We apply a number of classical metrics in an attempt to investigate their appropriateness for ranking ontologies, and compare the results with a questionnaire-based human study. Our results show that AKTiveRank will have great utility although there is potential for improvement

    A Semantic Similarity Measurement Method Based on Information Quality in the Structure of the Gene Ontology

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    Gene ontology (GO) which described a biological concept of gene has attracted attention as an index for measuring semantic similarity of gene. This paper considers a new method for measuring the semantic similarity of GO through an extension and combination of two existing methods by Resnik and Wang et al. in order to improve their drawbacks of effects of shallow annotation. It is shown that the proposed method is superior to existing methods through experiments with pathway data

    Using distributional similarity to organise biomedical terminology

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    We investigate an application of distributional similarity techniques to the problem of structural organisation of biomedical terminology. Our application domain is the relatively small GENIA corpus. Using terms that have been accurately marked-up by hand within the corpus, we consider the problem of automatically determining semantic proximity. Terminological units are dened for our purposes as normalised classes of individual terms. Syntactic analysis of the corpus data is carried out using the Pro3Gres parser and provides the data required to calculate distributional similarity using a variety of dierent measures. Evaluation is performed against a hand-crafted gold standard for this domain in the form of the GENIA ontology. We show that distributional similarity can be used to predict semantic type with a good degree of accuracy
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