Predicting the insurgence of human genetic diseases associated to single point protein mutations with support vector machines and evolutionary information

Bioinformatics. 2006 Nov 15;22(22):2729-34. doi: 10.1093/bioinformatics/btl423. Epub 2006 Aug 7.


Motivation: Human single nucleotide polymorphisms (SNPs) are the most frequent type of genetic variation in human population. One of the most important goals of SNP projects is to understand which human genotype variations are related to Mendelian and complex diseases. Great interest is focused on non-synonymous coding SNPs (nsSNPs) that are responsible of protein single point mutation. nsSNPs can be neutral or disease associated. It is known that the mutation of only one residue in a protein sequence can be related to a number of pathological conditions of dramatic social impact such as Alzheimer's, Parkinson's and Creutzfeldt-Jakob's diseases. The quality and completeness of presently available SNPs databases allows the application of machine learning techniques to predict the insurgence of human diseases due to single point protein mutation starting from the protein sequence.

Results: In this paper, we develop a method based on support vector machines (SVMs) that starting from the protein sequence information can predict whether a new phenotype derived from a nsSNP can be related to a genetic disease in humans. Using a dataset of 21 185 single point mutations, 61% of which are disease-related, out of 3587 proteins, we show that our predictor can reach more than 74% accuracy in the specific task of predicting whether a single point mutation can be disease related or not. Our method, although based on less information, outperforms other web-available predictors implementing different approaches.

Availability: A beta version of the web tool is available at

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Computational Biology / methods*
  • Databases, Protein
  • Evolution, Molecular*
  • Genetic Diseases, Inborn / genetics*
  • Genetic Predisposition to Disease*
  • Genetic Variation
  • Humans
  • Mutation
  • Phenotype
  • Point Mutation*
  • Polymorphism, Genetic
  • Polymorphism, Single Nucleotide*
  • Probability
  • Proteins / chemistry
  • Proteins / genetics*


  • Proteins