title: A novel dysregulated pathway-identification analysis based on global influence of within-pathway effects and crosstalk between pathways.
abstract: Identifying dysregulated pathways from high-throughput experimental data in order to infer underlying biological insights is an important task. Current pathway-identification methods focus on single pathways in isolation; however, consideration of crosstalk between pathways could improve our understanding of alterations in biological states. We propose a novel method of pathway analysis based on global influence (PAGI) to identify dysregulated pathways, by considering both within-pathway effects and crosstalk between pathways. We constructed a global gene–gene network based on the relationships among genes extracted from a pathway database. We then evaluated the extent of differential expression for each gene, and mapped them to the global network. The random walk with restart algorithm was used to calculate the extent of genes affected by global influence. Finally, we used cumulative distribution functions to determine the significance values of the dysregulated pathways. We applied the PAGI method to five cancer microarray datasets, and compared our results with gene set enrichment analysis and five other methods. Based on these analyses, we demonstrated that PAGI can effectively identify dysregulated pathways associated with cancer, with strong reproducibility and robustness. We implemented PAGI using the freely available R-based and Web-based tools (http://bioinfo.hrbmu.edu.cn/PAGI).
authors.forename: Junwei
authors.initials: J
authors.lastname: Han
authors.forename: Chunquan
authors.initials: C
authors.lastname: Li
authors.forename: Haixiu
authors.initials: H
authors.lastname: Yang
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Xu
authors.forename: Chunlong
authors.initials: C
authors.lastname: Zhang
authors.forename: Jiquan
authors.initials: J
authors.lastname: Ma
authors.forename: Xinrui
authors.initials: X
authors.lastname: Shi
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Desi
authors.initials: D
authors.lastname: Shang
authors.forename: Qianlan
authors.initials: Q
authors.lastname: Yao
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Zhang
authors.forename: Fei
authors.initials: F
authors.lastname: Su
authors.forename: Li
authors.initials: L
authors.lastname: Feng
authors.forename: Xia
authors.initials: X
authors.lastname: Li
mesh_terms: D000465:Algorithms; D019295:Computational Biology / Q000379:methods*; D030541:Databases, Genetic; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D007328:Insulin / Q000378:metabolism; D020407:Internet; D008954:Models, Biological; D009369:Neoplasms / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics
chemical_list: D007328:Insulin