title: Protein sector analysis for the clustering of disease-associated mutations.
abstract: BACKGROUND
  The importance of mutations in disease phenotype has been studied, with information available in databases such as OMIM. However, it remains a research challenge for the possibility of clustering amino acid residues based on an underlying interaction, such as co-evolution, to understand how mutations in these related sites can lead to different disease phenotypes.
  
  
  RESULTS
  This paper presents an integrative approach to identify groups of co-evolving residues, known as protein sectors. By studying a protein family using multiple sequence alignments and statistical coupling analysis, we attempted to determine if it is possible that these groups of residues could be related to disease phenotypes. After the protein sectors were identified, disease-associated residues within these groups of amino acids were mapped to a structure representing the protein family. In this study, we used the proposed pipeline to analyze two test cases of spermine synthase and Rab GDP dissociation inhibitor.
  
  
  CONCLUSIONS
  The results suggest that there is a possible link between certain groups of co-evolving residues and different disease phenotypes. The pipeline described in this work could also be used to study other protein families associated with human diseases.
authors.forename: Jose
authors.initials: J
authors.lastname: Guevara-Coto
authors.forename: Charles E
authors.initials: CE
authors.lastname: Schwartz
authors.forename: Liangjiang
authors.initials: L
authors.lastname: Wang
mesh_terms: D000596:Amino Acids / Q000235:genetics; D016000:Cluster Analysis; D004194:Disease / Q000235:genetics*; D019143:Evolution, Molecular; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000235:genetics; D006801:Humans; D038901:X-Linked Intellectual Disability / Q000235:genetics; D009154:Mutation; D010641:Phenotype; D011506:Proteins / Q000235:genetics*; D020539:Sequence Analysis, Protein; D013097:Spermine Synthase / Q000235:genetics
chemical_list: D000596:Amino Acids; D020730:Guanine Nucleotide Dissociation Inhibitors; D011506:Proteins; D013097:Spermine Synthase