Advertisement

HLA Typing pp 275-284 | Cite as

HLA Haplotype Frequency Estimation from Real-Life Data with the Hapl-o-Mat Software

  • Jürgen SauterEmail author
  • Christian Schäfer
  • Alexander H. Schmidt
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1802)

Abstract

HLA haplotype frequencies are of use in a variety of settings. Such data is typically derived either from family pedigree data by targeted typing or statistical analysis of large population-specific genotype samples. As established tools for the latter approach lacked ability to treat the amount, ambiguity, and inhomogeneity found in genotype data in hematopoietic stem cell donor registries, we developed Hapl-o-Mat to alleviate these specific shortcomings.

Keywords

HLA Immunogenetics Population genetics Bioinformatics Haplotype Expectation-maximization algorithm Open-source software 

References

  1. 1.
    Crawford DC, Nickerson DA (2005) Definition and clinical importance of haplotypes. Annu Rev Med 56:303–320.  https://doi.org/10.1146/annurev.med.56.082103.104540CrossRefPubMedGoogle Scholar
  2. 2.
    Harding RM, Fullerton SM, Griffiths RC, Bond J, Cox MJ, Schneider JA, Moulin DS, Clegg JB (1997) Archaic African and Asian lineages in the genetic ancestry of modern humans. Am J Hum Genet 60(4):772–789PubMedPubMedCentralGoogle Scholar
  3. 3.
    Hurley CK, Fernandez Vina M, Setterholm M (2003) Maximizing optimal hematopoietic stem cell donor selection from registries of unrelated adult volunteers. Tissue Antigens 61(6):415–424CrossRefPubMedGoogle Scholar
  4. 4.
    Schmidt AH, Sauter J, Pingel J, Ehninger G (2014) Toward an optimal global stem cell donor recruitment strategy. PLoS One 9(1):e86605.  https://doi.org/10.1371/journal.pone.0086605CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Eberhard HP, Feldmann U, Bochtler W, Baier D, Rutt C, Schmidt AH, Muller CR (2010) Estimating unbiased haplotype frequencies from stem cell donor samples typed at heterogeneous resolutions: a practical study based on over 1 million German donors. Tissue Antigens 76(5):352–361.  https://doi.org/10.1111/j.1399-0039.2010.01518.xCrossRefPubMedGoogle Scholar
  6. 6.
    Steiner D (2012) Computer algorithms in the search for unrelated stem cell donors. Bone Marrow Res 2012:175419.  https://doi.org/10.1155/2012/175419CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Bochtler W, Gragert L, Patel ZI, Robinson J, Steiner D, Hofmann JA, Pingel J, Baouz A, Melis A, Schneider J, Eberhard HP, Oudshoorn M, Marsh SG, Maiers M, Muller CR (2016) A comparative reference study for the validation of HLA-matching algorithms in the search for allogeneic hematopoietic stem cell donors and cord blood units. Hla 87(6):439–448.  https://doi.org/10.1111/tan.12817CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Marsh SGE, Albert ED, Bodmer WF, Bontrop RE, Dupont B, Erlich HA, Fernandez-Vina M, Geraghty DE, Holdsworth R, Hurley CK, Lau M, Lee KW, Mach B, Maiers M, Mayr WR, Muller CR, Parham P, Petersdorf EW, Sasazuki T, Strominger JL, Svejgaard A, Terasaki PI, Tiercy JM, Trowsdale J (2010) Nomenclature for factors of the HLA system, 2010. Tissue Antigens 75(4):291–455.  https://doi.org/10.1111/j.1399-0039.2010.01466.xCrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Schäfer C, Schmidt AH, Sauter J (2017) Hapl-o-mat: open-source software for HLA haplotype frequency estimation from ambiguous and heterogeneous data. BMC Bioinformatics 18(1):284.  https://doi.org/10.1186/s12859-017-1692-yCrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Dempster AP, Laird NM, Rubin DB (1977) Maximum likelihood from incomplete data via the EM algorithm. J R Stat Soc Series B (Methodological) 39(1):1–38Google Scholar
  11. 11.
    Excoffier L, Slatkin M (1995) Maximum-likelihood estimation of molecular haplotype frequencies in a diploid population. Mol Biol Evol 12(5):921–927PubMedGoogle Scholar
  12. 12.
    Long JC, Williams RC, Urbanek M (1995) An E-M algorithm and testing strategy for multiple-locus haplotypes. Am J Hum Genet 56(3):799–810PubMedPubMedCentralGoogle Scholar
  13. 13.
    Polańska J (2003) The EM algorithm and its implementation for the estimation of frequencies of SNP-haplotypes. Int J Appl Marth Comp Sci 13(3):419–429Google Scholar
  14. 14.
    NMDP (2016) Allele code lists. National marrow donor program. https://bioinformatics.bethematchclinical.org/HLA-Resources/Allele-Codes/Allele-Code-Lists/. 2016
  15. 15.
    Milius RP, Mack SJ, Hollenbach JA, Pollack J, Heuer ML, Gragert L, Spellman S, Guethlein LA, Trachtenberg EA, Cooley S, Bochtler W, Mueller CR, Robinson J, Marsh SGE, Maiers M (2013) Genotype list string: a grammar for describing HLA and KIR genotyping results in a text string. Tissue Antigens 82(2):106–112.  https://doi.org/10.1111/tan.12150CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Schmidt AH, Baier D, Solloch UV, Stahr A, Cereb N, Wassmuth R, Ehninger G, Rutt C (2009) Estimation of high-resolution HLA-A, -B, -C, -DRB1 allele and haplotype frequencies based on 8862 German stem cell donors and implications for strategic donor registry planning. Hum Immunol 70(11):895–902.  https://doi.org/10.1016/j.humimm.2009.08.006CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Jürgen Sauter
    • 1
    Email author
  • Christian Schäfer
    • 1
  • Alexander H. Schmidt
    • 1
  1. 1.DKMS gemeinnützige GmbHTübingenGermany

Personalised recommendations