Dataset Information

Evaluation of GO-based functional similarity measures using S. cerevisiae protein interaction and expression profile data.

ABSTRACT: BACKGROUND: Researchers interested in analysing the expression patterns of functionally related genes usually hope to improve the accuracy of their results beyond the boundaries of currently available experimental data. Gene ontology (GO) data provides a novel way to measure the functional relationship between gene products. Many approaches have been reported for calculating the similarities between two GO terms, known as semantic similarities. However, biologists are more interested in the relationship between gene products than in the scores linking the GO terms. To highlight the relationships among genes, recent studies have focused on functional similarities. RESULTS: In this study, we evaluated five functional similarity methods using both protein-protein interaction (PPI) and expression data of S. cerevisiae. The receiver operating characteristics (ROC) and correlation coefficient analysis of these methods showed that the maximum method outperformed the other methods. Statistical comparison of multiple- and single-term annotated proteins in biological process ontology indicated that genes with multiple GO terms may be more reliable for separating true positives from noise. CONCLUSION: This study demonstrated the reliability of current approaches that elevate the similarity of GO terms to the similarity of proteins. Suggestions for further improvements in functional similarity analysis are also provided.

SUBMITTER: Xu T

PROVIDER: S-EPMC2612010 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature

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Evaluation of GO-based functional similarity measures using S. cerevisiae protein interaction and expression profile data.

Xu Tao T Du Linfang L Zhou Yan Y

BMC bioinformatics 20081106

<h4>Background</h4>Researchers interested in analysing the expression patterns of functionally related genes usually hope to improve the accuracy of their results beyond the boundaries of currently available experimental data. Gene ontology (GO) data provides a novel way to measure the functional relationship between gene products. Many approaches have been reported for calculating the similarities between two GO terms, known as semantic similarities. However, biologists are more interested in t ...[more]

PMID: 18986551

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Project description:BackgroundBiological knowledge, and therefore Gene Ontology annotation sets, for human genes is incomplete. Recent studies have reported that biases in available GO annotations result in biased estimates of functional similarities of genes, but it is still unclear what the effect of incompleteness itself may be, even in the absence of bias. Pairwise gene similarities are used in a number of contexts, including gene "functional similarity" clustering and the related problem of functional ontology structure inference, but it is not known how different similarity measures or clustering methods perform on this task, and how the clusters are affected by annotation completeness.ResultsWe developed representations of both "complete" and "incomplete" GO annotation datasets based on experimentally-supported annotations from the GO database-specifically designed to model the incompleteness of human gene annotations-and computed semantic similarities for each set using a variety of different published measures. We then assessed the clusters derived from these measures using two different clustering methods: hierarchical clustering, and the CliXO algorithm. We find the CliXO algorithm, combined with appropriate measures, performs better than hierarchical clustering in reconstructing GO both when the data are complete, and incomplete. Some measures, particularly those that create a pairwise gene similarity by averaging over all pairwise annotation similarities, had consistently poor performance, and a few measures, such as Lin best-matched average and Relevance maximum, were generally among the best performers for a broad range in annotation completeness and types of GO classes. Finally, we show that for semantic similarity-based clustering, the multicellular organism process branch of the GO biological process ontology is more challenging to represent than the cellular process branch.ConclusionsWe assessed the effects of annotation completeness on the distribution of pairwise gene semantic similarity scores, and subsequent effects on the clusters derived from these scores. Our results suggest combinations of semantic similarity measures, gene-level scoring methods and clustering method that perform best for functional gene clustering using annotation sets of varying completeness. Overall, our results underscore the importance of increasing the completeness of GO annotations to for supporting computational analyses of gene function.

Project description:BACKGROUND:Interaction fingerprints (IFP) have been repeatedly shown to be valuable tools in virtual screening to identify novel hit compounds that can subsequently be optimized to drug candidates. As a complementary method to ligand docking, IFPs can be applied to quantify the similarity of predicted binding poses to a reference binding pose. For this purpose, a large number of similarity metrics can be applied, and various parameters of the IFPs themselves can be customized. In a large-scale comparison, we have assessed the effect of similarity metrics and IFP configurations to a number of virtual screening scenarios with ten different protein targets and thousands of molecules. Particularly, the effect of considering general interaction definitions (such as Any Contact, Backbone Interaction and Sidechain Interaction), the effect of filtering methods and the different groups of similarity metrics were studied. RESULTS:The performances were primarily compared based on AUC values, but we have also used the original similarity data for the comparison of similarity metrics with several statistical tests and the novel, robust sum of ranking differences (SRD) algorithm. With SRD, we can evaluate the consistency (or concordance) of the various similarity metrics to an ideal reference metric, which is provided by data fusion from the existing metrics. Different aspects of IFP configurations and similarity metrics were examined based on SRD values with analysis of variance (ANOVA) tests. CONCLUSION:A general approach is provided that can be applied for the reliable interpretation and usage of similarity measures with interaction fingerprints. Metrics that are viable alternatives to the commonly used Tanimoto coefficient were identified based on a comparison with an ideal reference metric (consensus). A careful selection of the applied bits (interaction definitions) and IFP filtering rules can improve the results of virtual screening (in terms of their agreement with the consensus metric). The open-source Python package FPKit was introduced for the similarity calculations and IFP filtering; it is available at: https://github.com/davidbajusz/fpkit .

Project description:BackgroundSerial Analysis of Gene Expression (SAGE) and microarrays have found a widespread application, but much ambiguity exists regarding the evaluation of these technologies. Cross-platform utilization of gene expression data from the SAGE and microarray technology could reduce the need for duplicate experiments and facilitate a more extensive exchange of data within the research community. This requires a measure for the correspondence of the different gene expression platforms. To date, a number of cross-platform evaluations (including a few studies using SAGE and Affymetrix GeneChips) have been conducted showing a variable, but overall low, concordance. This study evaluates these overall measures and introduces the between-ratio difference as a concordance measure pergene.ResultsIn this study, gene expression measurements of Unigene clusters represented by both Affymetrix GeneChips HG-U133A and SAGE were compared using two independent RNA samples. After matching of the data sets the final comparison contains a small data set of 1094 unique Unigene clusters, which is unbiased with respect to expression level. Different overall correlation approaches, like Up/Down classification, contingency tables and correlation coefficients were used to compare both platforms. In addition, we introduce a novel approach to compare two platforms based on the calculation of differences between expression ratios observed in each platform for each individual transcript. This approach results in a concordance measure per gene (with statistical probability value), as opposed to the commonly used overall concordance measures between platforms.ConclusionWe can conclude that intra-platform correlations are generally good, but that overall agreement between the two platforms is modest. This might be due to the binomially distributed sampling variation in SAGE tag counts, SAGE annotation errors and the intensity variation between probe sets of a single gene in Affymetrix GeneChips. We cannot identify or advice which platform performs better since both have their (dis)-advantages. Therefore it is strongly recommended to perform follow-up studies of interesting genes using additional techniques. The newly introduced between-ratio difference is a filtering-independent measure for between-platform concordance. Moreover, the between-ratio difference per gene can be used to detect transcripts with similar regulation on both platforms.

Dataset Information

Evaluation of GO-based functional similarity measures using S. cerevisiae protein interaction and expression profile data.

Publications

Evaluation of GO-based functional similarity measures using S. cerevisiae protein interaction and expression profile data.

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