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Centrality-based pathway enrichment: a systematic approach for finding significant pathways dominated by key genes

DOI: 10.1186/1752-0509-6-56

Keywords: Pathway enrichment, Biological network, Centrality, Gene expression data

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Abstract:

A systematic and extensible pathway enrichment method in which nodes are weighted by network centrality was proposed. We demonstrate how choice of pathway structure and centrality measurement, as well as the presence of key genes, affects pathway significance. We emphasize two improvements of our method over current methods. First, allowing for the diversity of genes’ characters and the difficulty of covering gene importance from all aspects, we set centrality as an optional parameter in the model. Second, nodes rather than genes form the basic unit of pathways, such that one node can be composed of several genes and one gene may reside in different nodes. By comparing our methodology to the original enrichment method using both simulation data and real-world data, we demonstrate the efficacy of our method in finding new pathways from biological perspective.Our method can benefit the systematic analysis of biological pathways and help to extract more meaningful information from gene expression data. The algorithm has been implemented as an R package CePa, and also a web-based version of CePa is provided.As omics and high throughput technology continues to develop, researchers can increasingly understand biological phenomena at the systems level; that is, can elucidate the complicated interactions between genes and molecules responsible for biological functions [1]. Microarray technology has been widely used to measure gene expression profiles and has produced huge amounts of data for biological analysis [2]. However, traditional single gene analysis tells us little about the cooperative roles of genes in real biological systems. New challenges for microarray data analysis are to find specific biological functions affected by a group of related genes. Biological pathways are sets of genes or molecules that act together by chemical reactions, molecule modifications or signalling transduction to carry out such functions [3]. Since pathways are essentially integrated ci

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