Dataset Information

GOAL: a software tool for assessing biological significance of genes groups.

ABSTRACT:

Background

Modern high throughput experimental techniques such as DNA microarrays often result in large lists of genes. Computational biology tools such as clustering are then used to group together genes based on their similarity in expression profiles. Genes in each group are probably functionally related. The functional relevance among the genes in each group is usually characterized by utilizing available biological knowledge in public databases such as Gene Ontology (GO), KEGG pathways, association between a transcription factor (TF) and its target genes, and/or gene networks.

Results

We developed

Goal

Gene Ontology AnaLyzer, a software tool specifically designed for the functional evaluation of gene groups. GOAL implements and supports efficient and statistically rigorous functional interpretations of gene groups through its integration with available GO, TF-gene association data, and association with KEGG pathways. In order to facilitate more specific functional characterization of a gene group, we implement three GO-tree search strategies rather than one as in most existing GO analysis tools. Furthermore, GOAL offers flexibility in deployment. It can be used as a standalone tool, a plug-in to other computational biology tools, or a web server application.

Conclusion

We developed a functional evaluation software tool, GOAL, to perform functional characterization of a gene group. GOAL offers three GO-tree search strategies and combines its strength in function integration, portability and visualization, and its flexibility in deployment. Furthermore, GOAL can be used to evaluate and compare gene groups as the output from computational biology tools such as clustering algorithms.

SUBMITTER: Tchagang AB

PROVIDER: S-EPMC2873542 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature

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Publications

GOAL: a software tool for assessing biological significance of genes groups.

Tchagang Alain B AB Gawronski Alexander A Bérubé Hugo H Phan Sieu S Famili Fazel F Pan Youlian Y

BMC bioinformatics 20100506

<h4>Background</h4>Modern high throughput experimental techniques such as DNA microarrays often result in large lists of genes. Computational biology tools such as clustering are then used to group together genes based on their similarity in expression profiles. Genes in each group are probably functionally related. The functional relevance among the genes in each group is usually characterized by utilizing available biological knowledge in public databases such as Gene Ontology (GO), KEGG pathw ...[more]

PMID: 20459620

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Project description:MOTIVATION:The expansion of cancer genome sequencing continues to stimulate development of analytical tools for inferring relationships between somatic changes and tumor development. Pathway associations are especially consequential, but existing algorithms are demonstrably inadequate. METHODS:Here, we propose the PathScan significance test for the scenario where pathway mutations collectively contribute to tumor development. Its design addresses two aspects that established methods neglect. First, we account for variations in gene length and the consequent differences in their mutation probabilities under the standard null hypothesis of random mutation. The associated spike in computational effort is mitigated by accurate convolution-based approximation. Second, we combine individual probabilities into a multiple-sample value using Fisher-Lancaster theory, thereby improving differentiation between a few highly mutated genes and many genes having only a few mutations apiece. We investigate accuracy, computational effort and power, reporting acceptable performance for each. RESULTS:As an example calculation, we re-analyze KEGG-based lung adenocarcinoma pathway mutations from the Tumor Sequencing Project. Our test recapitulates the most significant pathways and finds that others for which the original test battery was inconclusive are not actually significant. It also identifies the focal adhesion pathway as being significantly mutated, a finding consistent with earlier studies. We also expand this analysis to other databases: Reactome, BioCarta, Pfam, PID and SMART, finding additional hits in ErbB and EPHA signaling pathways and regulation of telomerase. All have implications and plausible mechanistic roles in cancer. Finally, we discuss aspects of extending the method to integrate gene-specific background rates and other types of genetic anomalies. AVAILABILITY:PathScan is implemented in Perl and is available from the Genome Institute at: http://genome.wustl.edu/software/pathscan.

Dataset Information

GOAL: a software tool for assessing biological significance of genes groups.

Background

Results

Goal

Conclusion

Publications

GOAL: a software tool for assessing biological significance of genes groups.

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