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Predicting pathogenicity of missense mutations

CREATED: 200808140308 Speaker: Shamil Sunyaev ** Genetic diagnostics

  • genetic data may inform clinical decisions
  • diagnostic by sequencing
  • large number of Variants of Unknown Significance (VUS)
  • bioinformatics method contribute with diagnostic of VUS if prediction accuracy would increase ** Rare variants in complex phenotypes
  • important to predict which variants are functional
  • rare variants can be used to predict new genes from all exon sequence data ** Evolutionary genomics
  • want to predict mutations of strong effect
  • abundance of weakly deleterious alleles in humans
  • weakly deleterious variants occur in highly conserved regions ** Predicting effect of missense mutations
  • most pathogenic mutations affect stability
  • hypermutability is a useful feature for predicting deleterious mutations
  • forward and backward selection, five-fold cross-validation, accuracy measured as AUC
  • naive bayes with discretization outperformed decision tree and SVM ** Training and testing
  • benign mutations: substitutions between close species, human polymorphism
  • damaging mutations

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