Pathway enrichment analysis with networks

Lu Liu, Jinmao Wei, Jianhua Ruan

    Research output: Contribution to journalArticlepeer-review

    7 Scopus citations

    Abstract

    Detecting associations between an input gene set and annotated gene sets (e.g., pathways) is an important problem in modern molecular biology. In this paper, we propose two algorithms, termed NetPEA and NetPEA’, for conducting network-based pathway enrichment analysis. Our algorithms consider not only shared genes but also gene–gene interactions. Both algorithms utilize a protein–protein interaction network and a random walk with a restart procedure to identify hidden relationships between an input gene set and pathways, but both use different randomization strategies to evaluate statistical significance and as a result emphasize different pathway properties. Compared to an over representation-based method, our algorithms can identify more statistically significant pathways. Compared to an existing network-based algorithm, EnrichNet, our algorithms have a higher sensitivity in revealing the true causal pathways while at the same time achieving a higher specificity. A literature review of selected results indicates that some of the novel pathways reported by our algorithms are biologically relevant and important. While the evaluations are performed only with KEGG pathways, we believe the algorithms can be valuable for general functional discovery from high-throughput experiments.

    Original languageEnglish (US)
    Article number246
    JournalGenes
    Volume8
    Issue number10
    DOIs
    StatePublished - Oct 2017

    Keywords

    • Enrichment analysis
    • Gene sets
    • Pathway
    • Protein–protein interaction network
    • Random walk with restart

    ASJC Scopus subject areas

    • Genetics
    • Genetics(clinical)

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