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Published on: October 27, 2017
A network-based pathway-extending approach using DNA methylation and gene expression data to identify altered
Jie Li1, Qiaosheng Zhang2,3, Zhuo Chen1
1Harbin Institute of Technology, School of Computer Science and Technology, Harbin, 150001, P.R. China.
Abstract:
Pathway analysis allows us to gain insights into a comprehensive understanding of the molecular mechanisms underlying cancers. Currently, high-throughput multi-omics data and various types of large-scale biological networks enable us to identify cancer-related pathways by comprehensively analyzing these data. Combining information from multidimensional data, pathway databases and interaction networks is a promising strategy to identify cancer-related pathways. Here we present a novel network-based approach for integrative analysis of DNA methylation and gene expression data to extend original pathways. The results show that the extension of original pathways can provide a basis for discovering new components of the original pathway and understanding the crosstalk between pathways in a large-scale biological network. By inputting the gene lists of the extended pathways into the classical gene set analysis (ORA and FCS), we effectively identified the altered pathways which are correlated well with the corresponding cancer. The method is evaluated on three datasets retrieved from TCGA (BRCA, LUAD and COAD). The results show that the integration of DNA methylation and gene expression data through a network of known gene interactions is effective in identifying altered pathways.
Insights
This study introduces a new network-based method to integrate DNA methylation and gene expression data for cancer pathway analysis. The approach effectively identifies altered cancer pathways by extending existing ones using gene interaction networks.
Area of Science:
- Bioinformatics
- Computational Biology
- Cancer Genomics
Background:
- Pathway analysis is crucial for understanding cancer molecular mechanisms.
- High-throughput multi-omics data and biological networks aid in identifying cancer-related pathways.
- Integrating multidimensional data, pathway databases, and interaction networks is a promising strategy.
Purpose of the Study:
- To present a novel network-based approach for the integrative analysis of DNA methylation and gene expression data.
- To extend original pathways by incorporating multi-omics information.
- To identify cancer-related altered pathways using this extended pathway information.
Main Methods:
- Developed a novel network-based approach for integrative analysis of DNA methylation and gene expression data.
- Extended original pathways using gene interaction networks.
- Applied classical gene set analysis (ORA and FCS) to extended pathway gene lists.
Main Results:
- Pathway extension provides a basis for discovering new pathway components.
- The method facilitates understanding crosstalk between pathways in large biological networks.
- Identified altered pathways correlated with specific cancers across TCGA datasets (BRCA, LUAD, COAD).
Conclusions:
- The integration of DNA methylation and gene expression data via gene interaction networks is effective for identifying altered cancer pathways.
- This network-based approach enhances pathway analysis for cancer research.
- The extended pathways offer deeper insights into cancer mechanisms and inter-pathway communication.
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