SNP-based imputation approaches for human leukocyte antigen (HLA) typing take advantage of the haplotype structure within the major histocompatibility complex (MHC) region. These methods predict HLA classical alleles using dense SNP genotypes, commonly found on array-based platforms used in genome-wide association studies (GWAS). The analysis of HLA classical alleles can be conducted on current SNP datasets at no additional cost. Here, we describe the workflow of HIBAG, an imputation method with attribute bagging, to infer a sample\'s HLA classical alleles using SNP data. Two examples are offered to demonstrate the functionality using public HLA and SNP data from the latest release of the 1000 Genomes project: genotype imputation using pre-built classifiers in a GWAS, and model training to create a new prediction model. The GPU implementation facilitates model building, making it hundreds of times faster compared to the single-threaded implementation.

The MHC/HLA region has been consistently associated with a large number of complex traits, including but not limited to, most immune-mediated ones. Efforts to pinpoint drivers of this commonly encountered association peak at the short arm of chromosome 6, however, have been challenging, owing to the high density of genes and the long and extended linkage disequilibrium that are characteristic of this region.The development of methods to impute classical HLA alleles and amino acids from SNP genotyping data has offered an important additional layer of information to the investigators seeking to fine map the signal in the region. As a result, imputation-aided association analyses are now typically employed to shed light on the relationship of this locus with disease susceptibility and response to drugs.In this chapter we discuss how the signal in the HLA region can be interrogated in practice, from performing the imputation to understanding its output and to incorporating it into downstream analysis. In addition, we recount some of the analytical approaches that are commonly used and suggest ways in which the findings from such imputation-aided analyses can be interpreted.

SNP-based imputation approaches for human leukocyte antigen (HLA) typing take advantage of the extended haplotype structure within the major histocompatibility complex (MHC) to predict classical HLA alleles using dense SNP genotypes, such as those available on chip panels of genome-wide association study (GWAS). These methods enable HLA analyses of classical alleles on existing SNP datasets genotyped in GWAS studies at no extra cost. Here, I describe the workflow of HIBAG, an imputation method with attribute bagging, for obtaining a sample\'s HLA class I and II genotypes of two-field resolution using SNP data. Two examples are provided to illustrate with a publicly available HLA and SNP dataset: genotype imputation with pre-fit classifiers in GWAS, and model training to build a new classifier.