Περίληψη:
Background and objectives: Next generation sequencing (NGS) has promising applications in transfusion medicine. Exome sequencing (ES) is increasingly used in the clinical setting, and blood group interpretation is an additional value that could be extracted from existing data sets. We provide the first release of an open-source software tailored for this purpose and describe its validation with three blood group systems. Materials and methods: The DTM-Tools algorithm was designed and used to analyse 1018 ES NGS files from the ClinSeq® cohort. Predictions were correlated with serology for 5 antigens in a subset of 108 blood samples. Discrepancies were investigated with alternative phenotyping and genotyping methods, including a long-read NGS platform. Results: Of 116 genomic variants queried, those corresponding to 18 known KEL, FY and JK alleles were identified in this cohort. 596 additional exonic variants were identified KEL, ACKR1 and SLC14A1, including 58 predicted frameshifts. Software predictions were validated by serology in 108 participants; one case in the FY blood group and three cases in the JK blood group were discrepant. Investigation revealed that these discrepancies resulted from (1) clerical error, (2) serologic failure to detect weak antigenic expression and (3) a frameshift variant absent in blood group databases. Conclusion: DTM-Tools can be employed for rapid Kell, Duffy and Kidd blood group antigen prediction from existing ES data sets; for discrepancies detected in the validation data set, software predictions proved accurate. DTM-Tools is open-source and in continuous development. © 2020 International Society of Blood Transfusion
Συγγραφείς:
Montemayor, C.
Simone, A.
Long, J.
Montemayor, O.
Delvadia, B.
Rivera, R.
Lewis, K.L.
Shahsavari, S.
Gandla, D.
Dura, K.
Krishnan, U.S.
Wendzel, N.C.
Elavia, N.
Grissom, S.
Karagianni, P.
Bueno, M.
Loy, D.
Cacanindin, R.
McLaughlin, S.
Tynuv, M.
Brunker, P.A.R.
Roback, J.
Adams, S.
Smith, H.
Biesecker, L.
Klein, H.G.
Λέξεις-κλειδιά:
blood group antigen; ACKR1 protein, human; blood group antigen; carrier protein; cell surface receptor; KEL protein, human; membrane protein; metalloproteinase; urea transporter, ACKR1 gene; algorithm; Article; blood group Duffy system; blood group Kell system; blood group Kidd system; blood sampling; data base; demography; DTM Tools database; frameshift mutation; gene; genetic variability; genotype; human; KEL gene; major clinical study; phenotype; priority journal; serology; SLC14A1 gene; software; whole exome sequencing; allele; blood group Duffy system; genetic variation; genetics; genotyping technique; high throughput sequencing; procedures; software; whole exome sequencing, Alleles; Blood Group Antigens; Duffy Blood-Group System; Genetic Variation; Genotyping Techniques; High-Throughput Nucleotide Sequencing; Humans; Membrane Glycoproteins; Membrane Transport Proteins; Metalloendopeptidases; Receptors, Cell Surface; Software; Whole Exome Sequencing
