A network-based pathway-expanding approach for pathway analysis.
BACKGROUND
Pathway analysis combining multiple types of high-throughput data, such as genomics and proteomics, has become the first choice to gain insights into the pathogenesis of complex diseases. Currently, several pathway analysis methods have been developed to study complex diseases. However, these methods did not take into account the interaction between internal and external genes of the pathway and between pathways. Hence, these approaches still face some challenges. Here, we propose a network-based pathway-expanding approach that takes the topological structures of biological networks into account.


RESULTS
First, two weighted gene-gene interaction networks (tumor and normal) are constructed integrating protein-protein interaction(PPI) information, gene expression data and pathway databases. Then, they are used to identify significant pathways through testing the difference of topological structures of expanded pathways in the two weighted networks. The proposed method is employed to analyze two breast cancer data. As a result, the top 15 pathways identified using the proposed method are supported by biological knowledge from the published literatures and other methods. In addition, the proposed method is also compared with other methods, such as GSEA and SPIA, and estimated using the classification performance of the top 15 expanded pathways.


CONCLUSIONS
A novel network-based pathway-expanding approach is proposed to avoid the limitations of existing pathway analysis approaches. Experimental results indicate that the proposed method can accurately and reliably identify significant pathways which are related to the corresponding disease.
School of Computer Science and Technology, Harbin Institute of Technology, West Da-Zhi Street, Harbin, China.|College of Science, Heilongjiang Bayi Agricultural University, Xinfeng Road, Daqing, China.
Qiaosheng
Q
Zhang
School of Computer Science and Technology, Harbin Institute of Technology, West Da-Zhi Street, Harbin, China. jieli@hit.edu.cn.
Jie
J
Li
School of Computer Science and Technology, Harbin Institute of Technology, West Da-Zhi Street, Harbin, China.
Haozhe
H
Xie
School of Computer Science and Technology, Harbin Institute of Technology, West Da-Zhi Street, Harbin, China.
Hanqing
H
Xue
School of Computer Science and Technology, Harbin Institute of Technology, West Da-Zhi Street, Harbin, China.
Yadong
Y
Wang
D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D016208:Databases, Factual; D005260:Female; D053263:Gene Regulatory Networks; D023281:Genomics / Q000379:methods*; D006801:Humans; D053858:Metabolic Networks and Pathways; D015398:Signal Transduction; D059467:Transcriptome
Network-based; Pathway analysis; Protein-protein interaction; Significant pathway