HLA-DRB1 and HLA-DQB1 alleles were imputed for asparaginase hypersensitivity studies. The HLA-DRB1 and HLA-DQB1 alleles of patients enrolled on either SJCRH or COG protocols were imputed to 4-digit resolution using SNP data from the patients and the T1DGC reference panel with both SNP data and 4-digit resolution HLA typing. (A) The discovery cohort consisting of SJCRH patients was used to identify associations between asparaginase hypersensitivity reactions and imputed HLA-DRB1 and/or HLA-DQB1 alleles. The validation cohort consisted of COG patients. (B) Using the imputed HLA-DRB1 alleles, the HLA-DRB1 amino acid sequence was inferred for every patient, and the association between polymorphic amino acids and asparaginase hypersensitivity reactions was determined. (C) Using the IEDB, imputed HLA alleles were scored for their binding affinity to E coli asparaginase peptide fragments. The imputed HLA alleles of patients were categorized into “high” or “low” binding categories for asparaginase, and the categories were tested for association with asparaginase hypersensitivity.