Differential network analysis for the identification of condition-specific pathway activity and regulation

Gennaro Gambardella, Maria Nicoletta Moretti, Rossella De Cegli, Luca Cardone, Adriano Peron, Diego Di Bernardo

Research output: Contribution to journalArticle

Abstract

Motivation: Identification of differential expressed genes has led to countless new discoveries. However, differentially expressed genes are only a proxy for finding dysregulated pathways. The problem is to identify how the network of regulatory and physical interactions rewires in different conditions or in disease.Results: We developed a procedure named DINA (DIfferential Network Analysis), which is able to identify set of genes, whose co-regulation is condition-specific, starting from a collection of condition-specific gene expression profiles. DINA is also able to predict which transcription factors (TFs) may be responsible for the pathway condition-specific co-regulation. We derived 30 tissue-specific gene networks in human and identified several metabolic pathways as the most differentially regulated across the tissues. We correctly identified TFs such as Nuclear Receptors as their main regulators and demonstrated that a gene with unknown function (YEATS2) acts as a negative regulator of hepatocyte metabolism. Finally, we showed that DINA can be used to make hypotheses on dysregulated pathways during disease progression. By analyzing gene expression profiles across primary and transformed hepatocytes, DINA identified hepatocarcinoma-specific metabolic and transcriptional pathway dysregulation.

Original languageEnglish
Pages (from-to)1776-1785
Number of pages10
JournalBioinformatics
Volume29
Issue number14
DOIs
Publication statusPublished - Jul 15 2013

ASJC Scopus subject areas

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

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  • Cite this

    Gambardella, G., Moretti, M. N., De Cegli, R., Cardone, L., Peron, A., & Di Bernardo, D. (2013). Differential network analysis for the identification of condition-specific pathway activity and regulation. Bioinformatics, 29(14), 1776-1785. https://doi.org/10.1093/bioinformatics/btt290