title: Evaluation of two methods for computational HLA haplotypes inference using a real dataset.
abstract: BACKGROUND
  HLA haplotype analysis has been used in population genetics and in the investigation of disease-susceptibility locus, due to its high polymorphism. Several methods for inferring haplotype genotypic data have been proposed, but it is unclear how accurate each of the methods is or which method is superior. The accuracy of two of the leading methods of computational haplotype inference--Expectation-Maximization algorithm based (implemented in Arlequin V3.0) and Bayesian algorithm based (implemented in PHASE V2.1.1)--was compared using a set of 122 HLA haplotypes (A-B-Cw-DQB1-DRB1) determined through direct counting. The accuracy was measured with the Mean Squared Error (MSE), Similarity Index (IF) and Haplotype Identification Index (IH).
  
  
  RESULTS
  None of the methods inferred all of the known haplotypes and some differences were observed in the accuracy of the two methods in terms of both haplotype determination and haplotype frequencies estimation. Working with haplotypes composed by low polymorphic sites, present in more than one individual, increased the confidence in the assignment of haplotypes and in the estimation of the haplotype frequencies generated by both programs.
  
  
  CONCLUSIONS
  The PHASE v2.1.1 implemented method had the best overall performance both in haplotype construction and frequency calculation, although the differences between the two methods were insubstantial. To our knowledge this was the first work aiming to test statistical methods using real haplotypic data from the HLA region.
authors.affiliation: Hospital Santo Espírito de Angra do Heroísmo, SEEBMO, Angra do Heroísmo, Azores, Portugal. bfbettencourt@seebmo.org
authors.forename: Bruno F
authors.initials: BF
authors.lastname: Bettencourt
authors.forename: Margarida R
authors.initials: MR
authors.lastname: Santos
authors.forename: Raquel N
authors.initials: RN
authors.lastname: Fialho
authors.forename: Ana R
authors.initials: AR
authors.lastname: Couto
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Peixoto
authors.forename: João P
authors.initials: JP
authors.lastname: Pinheiro
authors.forename: Hélder
authors.initials: H
authors.lastname: Spínola
authors.forename: Marian G
authors.initials: MG
authors.lastname: Mora
authors.forename: Cristina
authors.initials: C
authors.lastname: Santos
authors.forename: António
authors.initials: A
authors.lastname: Brehm
authors.forename: Jácome
authors.initials: J
authors.lastname: Bruges-Armas
mesh_terms: D000465:Algorithms; D004252:DNA Mutational Analysis / Q000379:methods*; D006680:HLA Antigens / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA / Q000379:methods*
chemical_list: D006680:HLA Antigens