title: Mutual information estimation reveals global associations between stimuli and biological processes.
abstract: BACKGROUND
  Although microarray gene expression analysis has become popular, it remains difficult to interpret the biological changes caused by stimuli or variation of conditions. Clustering of genes and associating each group with biological functions are often used methods. However, such methods only detect partial changes within cell processes. Herein, we propose a method for discovering global changes within a cell by associating observed conditions of gene expression with gene functions.
  
  
  RESULTS
  To elucidate the association, we introduce a novel feature selection method called Least-Squares Mutual Information (LSMI), which computes mutual information without density estimaion, and therefore LSMI can detect nonlinear associations within a cell. We demonstrate the effectiveness of LSMI through comparison with existing methods. The results of the application to yeast microarray datasets reveal that non-natural stimuli affect various biological processes, whereas others are no significant relation to specific cell processes. Furthermore, we discover that biological processes can be categorized into four types according to the responses of various stimuli: DNA/RNA metabolism, gene expression, protein metabolism, and protein localization.
  
  
  CONCLUSIONS
  We proposed a novel feature selection method called LSMI, and applied LSMI to mining the association between conditions of yeast and biological processes through microarray datasets. In fact, LSMI allows us to elucidate the global organization of cellular process control.
authors.affiliation: Department of Mathematical Informatics, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan. s-taiji@stat.t.u-tokyo.ac.jp
authors.forename: Taiji
authors.initials: T
authors.lastname: Suzuki
authors.forename: Masashi
authors.initials: M
authors.lastname: Sugiyama
authors.forename: Takafumi
authors.initials: T
authors.lastname: Kanamori
authors.forename: Jun
authors.initials: J
authors.lastname: Sese
mesh_terms: D000465:Algorithms; D001686:Biological Phenomena; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods*; D030541:Databases, Genetic; D020869:Gene Expression Profiling / Q000379:methods; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*