title: A classification approach for genotyping viral sequences based on multidimensional scaling and linear discriminant analysis.
abstract: BACKGROUND
  Accurate classification into genotypes is critical in understanding evolution of divergent viruses. Here we report a new approach, MuLDAS, which classifies a query sequence based on the statistical genotype models learned from the known sequences. Thus, MuLDAS utilizes full spectra of well characterized sequences as references, typically of an order of hundreds, in order to estimate the significance of each genotype assignment.
  
  
  RESULTS
  MuLDAS starts by aligning the query sequence to the reference multiple sequence alignment and calculating the subsequent distance matrix among the sequences. They are then mapped to a principal coordinate space by multidimensional scaling, and the coordinates of the reference sequences are used as features in developing linear discriminant models that partition the space by genotype. The genotype of the query is then given as the maximum a posteriori estimate. MuLDAS tests the model confidence by leave-one-out cross-validation and also provides some heuristics for the detection of 'outlier' sequences that fall far outside or in-between genotype clusters. We have tested our method by classifying HIV-1 and HCV nucleotide sequences downloaded from NCBI GenBank, achieving the overall concordance rates of 99.3% and 96.6%, respectively, with the benchmark test dataset retrieved from the respective databases of Los Alamos National Laboratory.
  
  
  CONCLUSIONS
  The highly accurate genotype assignment coupled with several measures for evaluating the results makes MuLDAS useful in analyzing the sequences of rapidly evolving viruses such as HIV-1 and HCV. A web-based genotype prediction server is available at http://www.muldas.org/MuLDAS/.
authors: Department of Bioinformatics & Life Sciences, Soongsil University, Seoul, Korea.
authors: Jiwoong
authors: J
authors: Kim
authors: Yongju
authors: Y
authors: Ahn
authors: Kichan
authors: K
authors: Lee
authors: Sung Hee
authors: SH
authors: Park
authors: Sangsoo
authors: S
authors: Kim
mesh_terms: D000465:Algorithms; D001483:Base Sequence; D002965:Classification / Q000379:methods*; D016002:Discriminant Analysis; D015497:HIV-1 / Q000145:classification / Q000235:genetics; D016174:Hepacivirus / Q000145:classification / Q000235:genetics; D008957:Models, Genetic; D015233:Models, Statistical; D015999:Multivariate Analysis; D010802:Phylogeny; D016415:Sequence Alignment; D014780:Viruses / Q000145:classification* / Q000235:genetics