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.

LanguageEnglish (US)
Pages1541-1552
Number of pages12
JournalBioinformatics
Volume29
Issue number12
DOIs
StatePublished - Jun 15 2013

Profile

Multilayer
Genes
Gene
Breast Cancer
Breast Neoplasms
Transcription Factor
Transcription factors
Transcription Factors
Target
erbB-2 Genes
Systems Biology
Gene Regulatory Networks
Acclimatization
Arabidopsis Thaliana
Transcriptional Regulation
Arabidopsis
Gene Networks
Reverse Engineering
Phenotype
Reverse engineering

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. 2013 ; Vol. 29, No. 12. pp. 1541-1552
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