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Sci Rep. 2018 Aug 30;8(1):13085. doi: 10.1038/s41598-018-31396-4.

CEA: Combination-based gene set functional enrichment analysis.

Sun D1,2, Liu Y1,2, Zhang XS1, Wu LY3,4.

Author information

1
IAM, MADIS, NCMIS, Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing, 100190, China.
2
School of Mathematical Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China.
3
IAM, MADIS, NCMIS, Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing, 100190, China. lywu@amss.ac.cn.
4
School of Mathematical Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China. lywu@amss.ac.cn.

Abstract

Functional enrichment analysis is a fundamental and challenging task in bioinformatics. Most of the current enrichment analysis approaches individually evaluate functional terms and often output a list of enriched terms with high similarity and redundancy, which makes it difficult for downstream studies to extract the underlying biological interpretation. In this paper, we proposed a novel framework to assess the performance of combination-based enrichment analysis. Using this framework, we formulated the enrichment analysis as a multi-objective combinatorial optimization problem and developed the CEA (Combination-based Enrichment Analysis) method. CEA provides the whole landscape of term combinations; therefore, it is a good benchmark for evaluating the current state-of-the-art combination-based functional enrichment methods in a comprehensive manner. We tested the effectiveness of CEA on four published microarray datasets. Enriched functional terms identified by CEA not only involve crucial biological processes of related diseases, but also have much less redundancy and can serve as a preferable representation for the enriched terms found by traditional single-term-based methods. CEA has been implemented in the R package CopTea and is available at http://github.com/wulingyun/CopTea/.

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