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. 2015 Dec;76(12):963-74.
doi: 10.1016/j.humimm.2015.08.001. Epub 2015 Aug 28.

Histoimmunogenetics Markup Language 1.0: Reporting next generation sequencing-based HLA and KIR genotyping

Robert P Milius  1 , Michael Heuer  2 , Daniel Valiga  2 , Kathryn J Doroschak  2 , Caleb J Kennedy  2 , Yung-Tsi Bolon  2 , Joel Schneider  2 , Jane Pollack  2 , Hwa Ran Kim  3 , Nezih Cereb  3 , Jill A Hollenbach  4 , Steven J Mack  5 , Martin Maiers  2
Affiliations

Histoimmunogenetics Markup Language 1.0: Reporting next generation sequencing-based HLA and KIR genotyping

Robert P Milius et al. Hum Immunol. 2015 Dec.

Abstract

We present an electronic format for exchanging data for HLA and KIR genotyping with extensions for next-generation sequencing (NGS). This format addresses NGS data exchange by refining the Histoimmunogenetics Markup Language (HML) to conform to the proposed Minimum Information for Reporting Immunogenomic NGS Genotyping (MIRING) reporting guidelines (miring.immunogenomics.org). Our refinements of HML include two major additions. First, NGS is supported by new XML structures to capture additional NGS data and metadata required to produce a genotyping result, including analysis-dependent (dynamic) and method-dependent (static) components. A full genotype, consensus sequence, and the surrounding metadata are included directly, while the raw sequence reads and platform documentation are externally referenced. Second, genotype ambiguity is fully represented by integrating Genotype List Strings, which use a hierarchical set of delimiters to represent allele and genotype ambiguity in a complete and accurate fashion. HML also continues to enable the transmission of legacy methods (e.g. site-specific oligonucleotide, sequence-specific priming, and Sequence Based Typing (SBT)), adding features such as allowing multiple group-specific sequencing primers, and fully leveraging techniques that combine multiple methods to obtain a single result, such as SBT integrated with NGS.

Keywords: Data standards; Genotyping; HLA; HML; KIR; MIRING; NGS.

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Conflict of interest statement

Conflicts of Interest: There are no conflicts of interest.

Figures

Figure 1
Figure 1
HML overall structure
Figure 2
Figure 2
Header
Figure 3
Figure 3
Examples of how hmlid can be used
Figure 4
Figure 4
Examples of how reporting-center can be used
Figure 5
Figure 5
Typing methods & primary data
Figure 6
Figure 6
Allele Assignment
Figure 7
Figure 7
Example of how allele-assignment may be used with glstring
Figure 8
Figure 8
Consensus sequence
Figure 9
Figure 9
Examples of using reference-database and reference-sequence
Figure 10
Figure 10
Example of consensus-sequence-block with variants
See this image and copyright information in PMC

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