Integrative Network Component Analysis for Regulatory Network Reconstruction

  • Chen Wang
  • Jianhua Xuan
  • Li Chen
  • Po Zhao
  • Yue Wang
  • Robert Clarke
  • Eric P. Hoffman
Part of the Lecture Notes in Computer Science book series (LNCS, volume 4983)

Abstract

Network Component Analysis (NCA) has shown its effectiveness in regulator identification by inferring the transcription factor activity (TFA) when both microarray data and ChIP-on-chip data are available. However, the NCA scheme is not applicable to many biological studies due to the lack of complete ChIP-on-chip data. In this paper, we propose an integrative NCA (iNCA) approach to combine motif information, limited ChIP-on-chip data, and gene expression data for regulatory network inference. Specifically, a Bayesian framework is adopted to develop a novel strategy, namely stability analysis with topological sampling, to infer key TFAs and their downstream gene targets. The iNCA approach with stability analysis reduces the computational cost by avoiding a direct estimation of the high-dimensional distribution in a traditional Bayesian approach. Stability indices are designed to measure the goodness of the estimated TFAs and their connectivity strengths. The approach can also be used to evaluate the confidence level of different data sources, considering the inevitable inconsistency among the data sources. The iNCA approach has been applied to a time course microarray data set of muscle regeneration. The experimental results show that iNCA can effectively integrate motif information, ChIP-on-chip data and microarray data to identify key regulators and their gene targets in muscle regeneration. In particular, several identified TFAs like those of MyoD, myogenin and YY1 are well supported by biological experiments.

Keywords

Network component analysis gene regulatory networks microarray data analysis ChIP-on-chip muscle regeneration 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2008

Authors and Affiliations

  • Chen Wang
    • 1
  • Jianhua Xuan
    • 1
  • Li Chen
    • 1
  • Po Zhao
    • 2
  • Yue Wang
    • 1
  • Robert Clarke
    • 3
  • Eric P. Hoffman
    • 2
  1. 1.Department of Electrical and Computer EngineeringVirginia Polytechnic Institute and State UniversityArlingtonUSA
  2. 2.Research Center for Genetic MedicineChildren’s National Medical CenterWashingtonUSA
  3. 3.Departments of Oncology and Physiology & BiophysicsGeorgetown University School of MedicineWashingtonUSA

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