Annotation Concept Synthesis and Enrichment Analysis: a Logic-Based Approach to the Interpretation of High-Throughput Experiments

Annotation Concept Synthesis and Enrichment Analysis: a Logic-Based Approach to the Interpretation of High-Throughput Experiments

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dc.contributor.author Jiline, Mikhail
dc.contributor.author Matwin, Stan
dc.contributor.author Turcotte, Marcel
dc.date.accessioned 2011-10-04T18:09:37Z
dc.date.available 2011-10-04T18:09:37Z
dc.date.created 2011 en_US
dc.date.issued 2011-10-04
dc.identifier.other 10.1093/bioinformatics/btr337 en_US
dc.identifier.uri http://bioinformatics.oxfordjournals.org/content/27/17/2391 en_US
dc.identifier.uri http://hdl.handle.net/10393/20284
dc.description.abstract MOTIVATION: Annotation Enrichment Analysis (AEA) is a widely used analytical approach to process data generated by high-throughput genomic and proteomic experiments such as gene expression microarrays. The analysis uncovers and summarizes discriminating background information (e.g. GO annotations) for sets of genes identified by experiments (e.g. a set of differentially expressed genes, a cluster). The discovered information is utilized by human experts to find biological interpretations of the experiments. However, AEA isolates and tests for overrepresentation only individual annotation terms or groups of similar terms and is limited in its ability to uncover complex phenomena involving relationship between multiple annotation terms from various knowledge bases. Also, AEA assumes that annotations describe the whole object of interest, which makes it difficult to apply it to sets of compound objects (e.g. sets of protein-protein interactions) and to sets of objects having an internal structure (e.g. protein complexes). RESULTS: We propose a novel logic-based Annotation Concept Synthesis and Enrichment Analysis (ACSEA) approach. ACSEA fuses inductive logic reasoning with statistical inference to uncover more complex phenomena captured by the experiments. We evaluate our approach on large-scale datasets from several microarray experiments and on a clustered genome-wide genetic interaction network using different biological knowledge bases. The discovered interpretations have lower P-values than the interpretations found by AEA, are highly integrative in nature, and include analysis of quantitative and structured information present in the knowledge bases. The results suggest that ACSEA can boost effectiveness of the processing of high-throughput experiments. CONTACT: mjiline@site.uottawa.ca. en_US
dc.language.iso en en_US
dc.title Annotation Concept Synthesis and Enrichment Analysis: a Logic-Based Approach to the Interpretation of High-Throughput Experiments en_US
dc.type Article en_US

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