EXAMINE: A computational approach to reconstructing gene regulatory networks

Xutao Deng, Huimin Geng, Hesham Ali

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Reverse-engineering of gene networks using linear models often results in an underdetermined system because of excessive unknown parameters. In addition, the practical utility of linear models has remained unclear. We address these problems by developing an improved method, EXpression Array MINing Engine (EXAMINE), to infer gene regulatory networks from time-series gene expression data sets. EXAMINE takes advantage of sparse graph theory to overcome the excessive-parameter problem with an adaptive-connectivity model and fitting algorithm. EXAMINE also guarantees that the most parsimonious network structure will be found with its incremental adaptive fitting process. Compared to previous linear models, where a fully connected model is used, EXAMINE reduces the number of parameters by O(N), thereby increasing the chance of recovering the underlying regulatory network. The fitting algorithm increments the connectivity during the fitting process until a satisfactory fit is obtained. We performed a systematic study to explore the data mining ability of linear models. A guideline for using linear models is provided: If the system is small (3-20 elements), more than 90% of the regulation pathways can be determined correctly. For a large-scale system, either clustering is needed or it is necessary to integrate information in addition to expression profile. Coupled with the clustering method, we applied EXAMINE to rat central nervous system development (CNS) data with 112 genes. We were able to efficiently generate regulatory networks with statistically significant pathways that have been predicted previously.

Original languageEnglish (US)
Pages (from-to)125-136
Number of pages12
JournalBioSystems
Volume81
Issue number2
DOIs
StatePublished - Aug 2005

Keywords

  • EXAMINE
  • Gene regulatory network
  • Linear models
  • Reverse engineering

ASJC Scopus subject areas

  • Statistics and Probability
  • Modeling and Simulation
  • Biochemistry, Genetics and Molecular Biology(all)
  • Applied Mathematics

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