title: Potential protein activity modifications of amino acid variants in the human transcriptome.
abstract: BACKGROUND
  The occurrence of widespread RNA and DNA sequence differences in the human transcriptome was reported in 2011. Similar findings were described in a second independent publication on personal omics profiling investigating the occurrence of dynamic molecular and related medical phenotypes. The suggestion that the RNA sequence variation was likely to affect disease susceptibility prompted us to investigate with a range of algorithms the amino acid variants reported to be present in the identified peptides to determine if they might be disease-causing.
  
  
  RESULTS
  The predictive qualities of the different algorithms were first evaluated by using nonsynonymous single-base nucleotide polymorphism (nsSNP) datasets, using independently established data on amino acid variants in several proteins as well as data obtained by mutational mapping and modelling of binding sites in the human serotonin transporter protein (hSERT). Validation of the used predictive algorithms was at a 75% level. Using the same algorithms, we found that widespread RNA and DNA sequence differences were predicted to impair the function of the peptides in over 57% of cases.
  
  
  CONCLUSIONS
  Our findings suggest that a proportion of edited RNAs which serve as templates for protein synthesis is likely to modify protein function, possibly as an adaptive survival mechanism in response to environmental modifications.
authors: Data Mining Group, Institute of Automatic Control, Faculty of Automatic, Electronic and Computer Science, Silesian University of Technology, Gliwice, Poland.
authors: Joanna
authors: J
authors: Zyla
authors: Public Health England, Chilton, Didcot, United Kingdom.
authors: Robert A
authors: RA
authors: Bulman
authors: Public Health England, Chilton, Didcot, United Kingdom.
authors: Christophe
authors: C
authors: Badie
authors: Public Health England, Chilton, Didcot, United Kingdom.
authors: Simon D
authors: SD
authors: Bouffler
mesh_terms: D000465:Algorithms; D019943:Amino Acid Substitution; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000737:chemistry / Q000502:physiology*; D059467:Transcriptome
chemical_list: D011506:Proteins