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Sparse Decomposition of Gene Expression Data to Infer Transcriptional Modules Guided by Motif Information

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

Abstract

An important topic in computational biology is to identify transcriptional modules through sequence analysis and gene expression profiling. A transcriptional module is formed by a group of genes under control of one or several transcription factors (TFs) that bind to cis-regulatory elements in the promoter regions of those genes. In this paper, we develop an integrative approach, namely motif-guided sparse decomposition (mSD), to uncover transcriptional modules by combining motif information and gene expression data. The method exploits the interplay of co-expression and co-regulation to find regulated gene patterns guided by TF binding information. Specifically, a motif-guided clustering method is first developed to estimate transcription factor binding activities (TFBAs); sparse component analysis is then followed to further identify TFs’ target genes. The experimental results show that the mSD approach can successfully help uncover condition-specific transcriptional modules that may have important implications in endocrine therapy of breast cancer.

Keywords

Motif analysis sparse component analysis transcriptional modules gene regulatory networks estrogen receptor binding 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2008

Authors and Affiliations

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

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