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Open Access Highly Accessed Methodology article

Mining differential top-k co-expression patterns from time course comparative gene expression datasets

Yu-Cheng Liu12, Chun-Pei Cheng1 and Vincent S Tseng13*

Author Affiliations

1 Department of Computer Science and Information Engineering, National Cheng Kung University, No. 1, University Road, Tainan City 701, Taiwan R.O.C

2 Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, No. 1, University Road, Tainan City 701, Taiwan R.O.C

3 Institute of Medical Informatics, National Cheng Kung University, No. 1, University Road, Tainan City 701, Taiwan R.O.C

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BMC Bioinformatics 2013, 14:230  doi:10.1186/1471-2105-14-230

Published: 21 July 2013

Abstract

Background

Frequent pattern mining analysis applied on microarray dataset appears to be a promising strategy for identifying relationships between gene expression levels. Unfortunately, too many itemsets (co-expressed genes) are identified by this analysis method since it does not consider the importance of each gene within biological processes to a cellular response and does not take into account temporal properties under biological treatment-control matched conditions in a microarray dataset.

Results

We propose a method termed TIIM (Top-k Impactful Itemsets Miner), which only requires specifying a user-defined number k to explore the top k itemsets with the most significantly differentially co-expressed genes between 2 conditions in a time course. To give genes different weights, a table with impact degrees for each gene was constructed based on the number of neighboring genes that are differently expressed in the dataset within gene regulatory networks. Finally, the resulting top-k impactful itemsets were manually evaluated using previous literature and analyzed by a Gene Ontology enrichment method.

Conclusions

In this study, the proposed method was evaluated in 2 publicly available time course microarray datasets with 2 different experimental conditions. Both datasets identified potential itemsets with co-expressed genes evaluated from the literature and showed higher accuracies compared to the 2 corresponding control methods: i) performing TIIM without considering the gene expression differentiation between 2 different experimental conditions and impact degrees, and ii) performing TIIM with a constant impact degree for each gene. Our proposed method found that several new gene regulations involved in these itemsets were useful for biologists and provided further insights into the mechanisms underpinning biological processes. The Java source code and other related materials used in this study are available at “http://websystem.csie.ncku.edu.tw/TIIM_Program.rar webcite”.