title: Prediction of stone disease by discriminant analysis and artificial neural networks in genetic polymorphisms: a new method.
abstract: OBJECTIVE
  To use information from genetic polymorphisms and from patients (drinking/exercise habits) to identify their association with stone disease, the main analytical and predictive tools being discriminant analysis (DA) and artificial neural networks (ANNs).
  
  
  METHODS
  Urinary stone disease is common in Taiwan; the formation of calcium oxalate stone is reportedly associated with genetic polymorphisms but there are many of these. Genotyping requires many individuals and markers because of the complexity of gene-gene and gene-environmental factor interactions. With the development of artificial intelligence, data-mining tools like ANNs can be used to derive more from patient data in predicting disease. Thus we compared 151 patients with calcium oxalate stones and 105 healthy controls for the presence of four genetic polymorphisms; cytochrome p450c17, E-cadherin, urokinase and vascular endothelial growth factor (VEGF). Information about environmental factors, e.g. water, milk and coffee consumption, and outdoor activities, was also collected. Stepwise DA and ANNs were used as classification methods to obtain an effective discriminant model.
  
  
  RESULTS
  With only the genetic variables, DA successfully classified 64% of the participants, but when all related factors (gene and environmental factors) were considered simultaneously, stepwise DA was successful in classifying 74%. The results for DA were best when six variables (sex, VEGF, stone number, coffee, milk, outdoor activities), found by iterative selection, were used. The ANN successfully classified 89% of participants and was better than DA when considering all factors in the model. A sensitivity analysis of the input parameters for ANN was conducted after the ANN program was trained; the most important inputs affecting stone disease were genetic (VEGF), while the second and third were water and milk consumption.
  
  
  CONCLUSIONS
  While data-mining tools such as DA and ANN both provide accurate results for assessing genetic markers of calcium stone disease, the ANN provides a better prediction than the DA, especially when considering all (genetic and environmental) related factors simultaneously. This model provides a new way to study stone disease in combination with genetic polymorphisms and environmental factors.
authors.affiliation: Ching Yun Institute of Technology, Chungli, Taiwan.
authors.forename: D
authors.initials: D
authors.lastname: Chiang
authors.forename: H-C
authors.initials: HC
authors.lastname: Chiang
authors.forename: W-C
authors.initials: WC
authors.lastname: Chen
authors.forename: F-J
authors.initials: FJ
authors.lastname: Tsai
mesh_terms: D000328:Adult; D000368:Aged; D016002:Discriminant Analysis; D016228:Endothelial Growth Factors / Q000235:genetics; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008222:Lymphokines / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016571:Neural Networks, Computer; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012680:Sensitivity and Specificity; D014545:Urinary Calculi / Q000175:diagnosis* / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors