Integrating gene expression and protein-protein interaction network to prioritize cancer-associated genes

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Abstract

Background: To understand the roles they play in complex diseases, genes need to be investigated in the networks they are involved in. Integration of gene expression and network data is a promising approach to prioritize disease-associated genes. Some methods have been developed in this field, but the problem is still far from being solved.Results: In this paper, we developed a method, Networked Gene Prioritizer (NGP), to prioritize cancer-associated genes. Applications on several breast cancer and lung cancer datasets demonstrated that NGP performs better than the existing methods. It provides stable top ranking genes between independent datasets. The top-ranked genes by NGP are enriched in the cancer-associated pathways. The top-ranked genes by NGP-PLK1, MCM2, MCM3, MCM7, MCM10 and SKP2 might coordinate to promote cell cycle related processes in cancer but not normal cells.Conclusions: In this paper, we have developed a method named NGP, to prioritize cancer-associated genes. Our results demonstrated that NGP performs better than the existing methods. © 2012 Wu et al.; licensee BioMed Central Ltd.

Figures

  • Table 1 The top 10 genes of different methods in breast cancer patient datasets
  • Table 2 Pathways that the top ranking genes of different methods are enriched in in breast cancer patient datasets
  • Table 3 The top 10 genes of different methods in NSCLC patient datasets
  • Figure 1 PLK1-MCM complex-SKP2 subnet in breast cancer patient datasets.
  • Figure 2 PLK1-MCM complex-SKP2 subnet in NSCLC patient datasets.
  • Figure 3 Expression correlation and differential expression of genes in the PLK1-MCM complex-SKP2 subnets. A, In NGP-ND, PPIs are weighted by the absolute average of Spearman coefficient of interacting genes’ expression in ER positive and ER negative samples. The weights of all the PPIs in the PLK1-MCM complex-SKP2 subnet of breast cancer patient datasets are displayed. B, In NGP-NR, PPIs are weighted by the absolute difference of Spearman coefficient of interacting genes’ expression in lung cancer and normal samples. The weights of all the PPIs in the PLK1-MCM complex-SKP2 subnet of NSCLC patient datasets are displayed. C, The differential expression of genes in the PLK1-MCM complex-SKP2 subnet of breast cancer patient datasets is displayed by –log(p), where p is estimated by t test. Genes that are up regulated and down regulated in ER negative samples are displayed in upper and lower right quadrant, respectively. D, The differential expression of genes in the PLK1-MCM complex-SKP2 subnet of NSCLC patient datasets is displayed by –log (p). Genes that are up regulated and down regulated in lung cancer samples are displayed in upper and lower right quadrant, respectively.
  • Figure 4 Flowchart of NGP. PPI: protein-protein interaction; DE genes: differentially expressed genes.

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CITATION STYLE

APA

Wu, C., Zhu, J., & Zhang, X. (2012). Integrating gene expression and protein-protein interaction network to prioritize cancer-associated genes. BMC Bioinformatics, 13(1). https://doi.org/10.1186/1471-2105-13-182

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