A community standard for immunogenomic data reporting and analysis: proposal for a STrengthening the REporting of Immunogenomic Studies statement

Abstract

Modern high-throughput HLA and KIR typing technologies are generating a wealth of immunogenomic data with the potential to revolutionize the fields of histocompatibility and immune-related disease association and population genetic research, much as SNP-based approaches have revolutionized association research. The STrengthening the REporting of Genetic Association studies (STREGA) statement provides community-based data reporting and analysis standards for genomic disease-association studies, identifying specific areas in which adoption of reporting guidelines can improve the consistent interpretation of genetic studies. While aspects of STREGA can be applied to immunogenomic studies, HLA and KIR research requires additional consideration, as the high levels of polymorphism associated with immunogenomic data pose unique methodological and computational challenges to the synthesis of information across datasets. Here, we outline the principle challenges to consistency in immunogenomic studies, and propose that an immunogenomic-specific analog to the STREGA statement, a STrengthening the REporting of Immunogenomic Studies (STREIS) statement, be developed as part of the 16th International HLA and Immunogenetics Workshop. We propose that STREIS extends at least four of the 22 elements of the STREGA statement to specifically address issues pertinent to immunogenomic data: HLA and KIR nomenclature, data-validation, ambiguity resolution, and the analysis of highly polymorphic genetic systems. As with the STREGA guidelines, the intent behind STREIS is not to dictate the design of immunogenomic studies, but to ensure consistent and transparent reporting of research, facilitating the synthesis of HLA and KIR data across studies.

Figure 1. Known, Unknown and Imputed Exon Sequences for Classical HLA Genes

Sequence categories for all HLA-A, B, C, DPA1, DPB1, DQA1, DQB1, DRB1, DRB3, DRB4, and DRB5 alleles in IMGT/HLA Database release 3.2.0 are color coded. Known sequences are shown in green, unknown sequences that are 5′ of the peptide binding domain (PBD) encoding exons (exons 2 and 3 for class I, and exon 2 for class II alleles) are shown in blue, imputed sequences that are 5′ of the PBD exons are shown in red, imputed sequences that are 3′ of the PBD exons are shown in purple, and unknown sequences that are 3′ of the PBD exons are shown in aqua. The horizontal scale indicates the distance in nucleotide bases from the start codon. A. Sequence categories for 4268 class I alleles over exons 1-8. B. Sequence categories for 1248 class II alleles over exons 1-6.