MIRING

The structure of the HLA typing report in this profile attempts to follow the principles outlined in the Minimum Information for ReportIng Next-generation sequence Genotyping (MIRING). These principles were identified through a series of meetings with an international group of stakeholders in the application of Next Generation Sequencing (NGS) technology for genotyping the HLA and KIR genes as well as other immune-related genes (http://igdawg.org/ngs.html). MIRING describes eight principles, described in detail in Human Immunology. 2015 Dec; 76(12):954-962. These include detailed metadata about:

1. MIRING Annotation
2. Reference Context
3. Full Genotype
4. Consensus Sequence
5. Novel Polymorphisms
6. Platform Documentation
7. Read Processing Documentation
8. Primary Data

These principles were implemented in a technical specification by extending an existing XML based format for exchanging histocompatibility and immunogenetic genotyping data called Histoimmunogenetics Markup Language (HML) to include results from NGS methodologies. The resulting schema may be found in here. The National Marrow Donor Program (NMDP)/Be The Match uses this format for reporting HLA genotyping from potential donors and for patients needing stem cell transplants.

Both MIRING and HML were used to inform mapping data elements to FHIR resources profiled in this IG. Examples are found at the end of this page.

• Minimum information for reporting next generation sequence genotyping (MIRING): Guidelines for reporting HLA and KIR genotyping via next generation sequencing (see here )
• Histoimmunogenetics Markup Language 1.0: Reporting Next Generation Sequencing-based HLA and KIR Genotyping (see here )

HLA - Nomenclature and Allele Assignment

Once HLA is typed, perhaps using targeted probes, exon sequencing, or full gene sequencing, the results are analyzed and assigned to one or more of the IMGT/HLA gene alleles using the HLA nomenclature. While the actual results may be a haplotype of exons or a set of partial gene sequences, the results are assigned to an allele from a known list. This allows results from different HLA genotyping methodologies to be compared, for example for donor/recipient transplant matching. However, reducing the results to HLA nomenclature may introduce ambiguity in the actual results. For example, an allele may be reported at only a two-field protein level (e.g., HLA-B*57:01) which represents any of over forty DNA variants, while the actual data may represent a single full gene (e.g., HLA-B*57:01:01:05). The nomenclature may also over represent the quality of the data. For example, when a full gene allele name is assigned to the results, it is unknown how the data was captured (probes, exon-only sequence, or full gene sequencing). Methodology is captured separately in the report. Also, this system cannot easily capture novel alleles as it represents a closed-world of possible alleles. Earlier scientific articles and data may reference HLA serotypes (e.g. HLA-B57), recognizable by the absence of an asterisk in the name, which does not capture any molcular information. The IMGT/HLA allele database is updated every three months to account for the discovery of new alleles, and the deletion or renaming of old alleles. This is why it is important to include the IMGT/HLA version when the HLA allele is assigned.