title: Comprehensive red blood cell and platelet antigen prediction from whole genome sequencing: proof of principle.
abstract: BACKGROUND
  There are 346 serologically defined red blood cell (RBC) antigens and 33 serologically defined platelet (PLT) antigens, most of which have known genetic changes in 45 RBC or six PLT genes that correlate with antigen expression. Polymorphic sites associated with antigen expression in the primary literature and reference databases are annotated according to nucleotide positions in cDNA. This makes antigen prediction from next-generation sequencing data challenging, since it uses genomic coordinates.
  
  
  METHODS
  The conventional cDNA reference sequences for all known RBC and PLT genes that correlate with antigen expression were aligned to the human reference genome. The alignments allowed conversion of conventional cDNA nucleotide positions to the corresponding genomic coordinates. RBC and PLT antigen prediction was then performed using the human reference genome and whole genome sequencing (WGS) data with serologic confirmation.
  
  
  RESULTS
  Some major differences and alignment issues were found when attempting to convert the conventional cDNA to human reference genome sequences for the following genes: ABO, A4GALT, RHD, RHCE, FUT3, ACKR1 (previously DARC), ACHE, FUT2, CR1, GCNT2, and RHAG. However, it was possible to create usable alignments, which facilitated the prediction of all RBC and PLT antigens with a known molecular basis from WGS data. Traditional serologic typing for 18 RBC antigens were in agreement with the WGS-based antigen predictions, providing proof of principle for this approach.
  
  
  CONCLUSIONS
  Detailed mapping of conventional cDNA annotated RBC and PLT alleles can enable accurate prediction of RBC and PLT antigens from whole genomic sequencing data.
authors.affiliation: Department of Pathology.|Harvard Medical School, Boston, Massachusetts.
authors.forename: William J
authors.initials: WJ
authors.lastname: Lane
authors.affiliation: New York Blood Center, New York, New York.
authors.forename: Connie M
authors.initials: CM
authors.lastname: Westhoff
authors.affiliation: Department of Pathology.
authors.forename: Jon Michael
authors.initials: JM
authors.lastname: Uy
authors.affiliation: Department of Pathology.
authors.forename: Maria
authors.initials: M
authors.lastname: Aguad
authors.affiliation: Department of Pathology.
authors.forename: Robin
authors.initials: R
authors.lastname: Smeland-Wagman
authors.affiliation: Department of Pathology.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Kaufman
authors.affiliation: Department of Pathology.|Harvard Medical School, Boston, Massachusetts.|Laboratory for Molecular Medicine.|Partners Healthcare Personalized Medicine, Boston, Massachusetts.
authors.forename: Heidi L
authors.initials: HL
authors.lastname: Rehm
authors.affiliation: Division of Genetics, Department of Medicine.|Harvard Medical School, Boston, Massachusetts.|Partners Healthcare Personalized Medicine, Boston, Massachusetts.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Green
authors.affiliation: Division of Transfusion Medicine, Department of Pathology, Brigham and Women's Hospital.
authors.forename: Leslie E
authors.initials: LE
authors.lastname: Silberstein
mesh_terms: D016824:Antigens, Human Platelet / Q000235:genetics*; D001789:Blood Group Antigens / Q000235:genetics*; D004912:Erythrocytes / Q000276:immunology; D023281:Genomics; D006801:Humans
chemical_list: D016824:Antigens, Human Platelet; D001789:Blood Group Antigens