Reconstruction of transcription regulatory networks by stability-based network component analysis

Xi Chen, Chen Wang, Ayesha N. Shajahan, Rebecca B. Riggins, Robert Clarke, Jianhua Xuan

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Reliable inference of transcription regulatory networks is still a challenging task in the field of computational biology. Network component analysis (NCA) has become a powerful scheme to uncover the networks behind complex biological processes, especially when gene expression data is integrated with binding motif information. However, the performance of NCA is impaired by the high rate of false connections in binding motif information and the high level of noise in gene expression data. Moreover, in real applications such as cancer research, the performance of NCA in simultaneously analyzing multiple candidate transcription factors (TFs) is further limited by the small sample number of gene expression data. In this paper, we propose a novel scheme, stability-based NCA, to overcome the above-mentioned problems by addressing the inconsistency between gene expression data and motif binding information (i.e., prior network knowledge). This method introduces small perturbations on prior network knowledge and utilizes the variation of estimated TF activities to reflect the stability of TF activities. Such a scheme is less limited by the sample size and especially capable to identify condition-specific TFs and their target genes. Experiment results on both simulation data and real breast cancer data demonstrate the efficiency and robustness of the proposed method.

Original languageEnglish (US)
Title of host publicationBioinformatics Research and Applications - 8th International Symposium, ISBRA 2012, Proceedings
Pages36-47
Number of pages12
DOIs
StatePublished - May 22 2012
Event8th International Symposium on Bioinformatics Research and Applications, ISBRA 2012 - Dallas, TX, United States
Duration: May 21 2012May 23 2012

Publication series

NameLecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
Volume7292 LNBI
ISSN (Print)0302-9743
ISSN (Electronic)1611-3349

Other

Other8th International Symposium on Bioinformatics Research and Applications, ISBRA 2012
CountryUnited States
CityDallas, TX
Period5/21/125/23/12

Keywords

  • network component analysis
  • stability analysis
  • target genes identification
  • transcription factor activity
  • transcription regulatory network

ASJC Scopus subject areas

  • Theoretical Computer Science
  • Computer Science(all)

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  • Cite this

    Chen, X., Wang, C., Shajahan, A. N., Riggins, R. B., Clarke, R., & Xuan, J. (2012). Reconstruction of transcription regulatory networks by stability-based network component analysis. In Bioinformatics Research and Applications - 8th International Symposium, ISBRA 2012, Proceedings (pp. 36-47). (Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics); Vol. 7292 LNBI). https://doi.org/10.1007/978-3-642-30191-9_4