title: Efficiently finding genome-wide three-way gene interactions from transcript- and genotype-data.
abstract: BACKGROUND
  We address the issue of finding a three-way gene interaction, i.e. two interacting genes in expression under the genotypes of another gene, given a dataset in which expressions and genotypes are measured at once for each individual. This issue can be a general, switching mechanism in expression of two genes, being controlled by categories of another gene, and finding this type of interaction can be a key to elucidating complex biological systems. The most suitable method for this issue is likelihood ratio test using logistic regressions, which we call interaction test, but a serious problem of this test is computational intractability at a genome-wide level.
  
  
  RESULTS
  We developed a fast method for this issue which improves the speed of interaction test by around 10 times for any size of datasets, keeping highly interacting genes with an accuracy of approximately 85%. We applied our method to approximately 3 x 10(8) three-way combinations generated from a dataset on human brain samples and detected three-way gene interactions with small P-values. To check the reliability of our results, we first conducted permutations by which we can show that the obtained P-values are significantly smaller than those obtained from permuted null examples. We then used GEO (Gene Expression Omnibus) to generate gene expression datasets with binary classes to confirm the detected three-way interactions by using these datasets and interaction tests. The result showed us some datasets with significantly small P-values, strongly supporting the reliability of the detected three-way interactions.
  
  
  BACKGROUND
  Software is available from http://www.bic.kyoto-u.ac.jp/pathway/kayano/bioinfo_three-way.html
  
  
  BACKGROUND
  kayano@kuicr.kyoto-u.ac.jp
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Bioinformatics Center, Institute for Chemical Research, Kyoto University, Gokasho, Uji 611-0011, Japan. kayano@kuicr.kyoto-u.ac.jp
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Kayano
authors.forename: Ichigaku
authors.initials: I
authors.lastname: Takigawa
authors.forename: Motoki
authors.initials: M
authors.lastname: Shiga
authors.forename: Koji
authors.initials: K
authors.lastname: Tsuda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mamitsuka
mesh_terms: D030541:Databases, Genetic; D015870:Gene Expression; D020869:Gene Expression Profiling / Q000379:methods*; D016678:Genome; D023281:Genomics / Q000379:methods*; D005838:Genotype; D016015:Logistic Models; D012984:Software