The content in this section has not undergone work group review and may be significantly revised prior to the next ballot.

This section covers additional guidelines related to genetic assessments related to the matching of donor and recipient tissue for donation, including bone marrow, organ and other tissue donations. In particular, it covers additional guidance related to reports dealing with HLA (Human Leukocyte Antigens) typing.

1.7.1 General guidance

While not specifically profiled in this version of the IG, some additional constraints will typically apply to somatic profiles. Patient will typically be mandatory as transplant genomics is not relevant for environmental samples.

1.7.2 HLA genotyping results profile

Human leukocyte antigen (HLA) genotyping is fundamental for research and clinical practice in immunogenetics and histocompatibility. Pointers to external locations refer to registered methods, raw NGS reads, and reference standards can be conveyed in this profile. Information about allele assignment including ambiguous results and the allele database used for assignments is stored in extensions.

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 international group of stakeholders in the application of Next Generation Sequencing (NGS) technology for genotyping the HLA and KIR loci as well as other immune-related loci (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 (https://bioinformatics.bethematchclinical.org/hla-resources/hml/). The resulting schema may be found in https://schemas.nmdp.org/. 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 such as Patient, Specimen, Sequence, Observation-Genetic Profile, and DiagnosticReport where possible. Several additional data elements were needed specifically for this use case, resulting in the development of a specific profile for reporting HLA genotyping results (Diagnostic Report Profile for HLA Genotyping Results).

• 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 )

The profiles for HLA genotyping have not yet been converted to align with the core profiles of this IG. This work will be completed prior to the August ballot cycle.

A first draft of a transaction bundle representing an HLA genotyping report using guidance of this IG can be found here.

1.7.3 Transplant-specific Genetic Interpretations

TODO

1.7.4 Transplant-specific Genetic Impacts

TODO

1.7.5 Transplant-specific Computable Genetic Findings

TODO

1.7.6 Transplant-specific Non-Computable Genetic Findings

TODO

1.7.7 Transplant-specific Guidance and Recommendations

TODO