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BMC Systems Biology

, 5:S10

First Online: 23 December 2011


BackgroundVarious gene-expression signatures for breast cancer are available for the prediction of clinical outcome. However due to small overlap between different signatures, it is challenging to integrate existing disjoint signatures to provide a unified insight on the association between gene expression and clinical outcome.

ResultsIn this paper, we propose a method to integrate different breast cancer gene signatures by using graph centrality in a context-constrained protein interaction network PIN. The context-constrained PIN for breast cancer is built by integrating complete PIN and various gene signatures reported in literatures. Then, we use graph centralities to quantify the importance of genes to breast cancer. Finally, we get reliable gene signatures that are consisted by the genes with high graph centrality. The genes which are well-known breast cancer genes, such as TP53 and BRCA1, are ranked extremely high in our results. Compared with previous results by functional enrichment analysis, graph centralities, especially the eigenvector centrality and subgraph centrality, based gene signatures are more tightly related to breast cancer. We validate these signatures on genome-wide microarray dataset and found strong association between the expression of these signature genes and pathologic parameters.

ConclusionsIn summary, graph centralities provide a novel way to connect different cancer signatures and to understand the mechanism of relationship between gene expression and clinical outcome of breast cancer. Moreover, this method is not only can be used on breast cancer, but also can be used on other gene expression related diseases and drug studies.

Electronic supplementary materialThe online version of this article doi:10.1186-1752-0509-5-S3-S10 contains supplementary material, which is available to authorized users.

Jianxin Wang, Gang Chen contributed equally to this work.

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Author: Jianxin Wang - Gang Chen - Min Li - Yi Pan


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