A multi-layer inference approach to reconstruct condition-specific genes and their regulation

Ming Wu, Li Liu, Hussein Hijazi, Christina Chan

    Research output: Contribution to journalArticle

    • 5 Citations

    Abstract

    An important topic in systems biology is the reverse engineering of regulatory mechanisms through reconstruction of context-dependent gene networks. A major challenge is to identify the genes and the regulations specific to a condition or phenotype, given that regulatory processes are highly connected such that a specific response is typically accompanied by numerous collateral effects. In this study, we design a multi-layer approach that is able to reconstruct condition-specific genes and their regulation through an integrative analysis of large-scale information of gene expression, protein interaction and transcriptional regulation (transcription factor-target gene relationships). We establish the accuracy of our methodology against synthetic datasets, as well as a yeast dataset. We then extend the framework to the application of higher eukaryotic systems, including human breast cancer and Arabidopsis thaliana cold acclimation. Our study identified TACSTD2 (TROP2) as a target gene for human breast cancer and discovered its regulation by transcription factors CREB, as well as NFkB. We also predict KIF2C is a target gene for ER-/HER2-breast cancer and is positively regulated by E2F1. The predictions were further confirmed through experimental studies.

    Original languageEnglish (US)
    Pages (from-to)1541-1552
    Number of pages12
    JournalBioinformatics
    Volume29
    Issue number12
    DOIs
    StatePublished - Jun 15 2013

    Profile

    Gene
    Genes
    Cyclic AMP Receptor Protein
    Breast Neoplasms
    Breast cancer
    Target
    Transcription Factors
    Datasets
    Transcription factor
    Multilayer
    Transcription factors
    erbB-2 Genes
    Systems Biology
    Gene Regulatory Networks
    Acclimatization
    Arabidopsis
    Yeasts
    Phenotype
    Gene Expression
    Proteins

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Computational Theory and Mathematics
    • Computer Science Applications
    • Computational Mathematics
    • Statistics and Probability
    • Medicine(all)

    Cite this

    A multi-layer inference approach to reconstruct condition-specific genes and their regulation. / Wu, Ming; Liu, Li; Hijazi, Hussein; Chan, Christina.

    In: Bioinformatics, Vol. 29, No. 12, 15.06.2013, p. 1541-1552.

    Research output: Contribution to journalArticle

    Wu, Ming; Liu, Li; Hijazi, Hussein; Chan, Christina / A multi-layer inference approach to reconstruct condition-specific genes and their regulation.

    In: Bioinformatics, Vol. 29, No. 12, 15.06.2013, p. 1541-1552.

    Research output: Contribution to journalArticle

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