TISSUE ANTIGENS COMMENTARY OUTLINE

• 1) The General Issue of Consistency in Genetic Studies
  
  • a) Consensus is emerging within the genomics community regarding the need for community data-reporting and analysis standards in genetic disease association studies
    
  • b) Examples, STREGA, STROBE, etc., under EQUATOR
    
  • c) Standards are needed to align immunogenomic research with the larger genomics community

• 2) Challenges to Consistency in Immunogenomic Data Management
  
  • a) HLA Nomenclature
    
    • i) Inconsistent adoption of historical changes
      
    • ii) April 2010 change in naming conventions to colon delimited fields
      
    • iii) Inconsistent formats for allele-name truncation
      
  • b) KIR nomenclature
    
    • i) Recording some alleles as independent loci
      
    • ii) No standard to account for locus-level copy number variants
      
    • iii) No means to identify chromosomal location of duplicates
      
  • c) Treatment of ambiguity in genotyping results
    
    • i) Major obstacle to combining data sets
      
      • (1) Allelic ambiguity
        
      • (2) Genotypic ambiguity
        
    • ii) No standard to resolve ambiguities
      
    • iii) No standard to record methods by which ambiguities are resolved
      
    • iv) Genotype ambiguity in patient/case populations
      
  • d) Maintaining long-term utility of genotype data in donor registries
    
    • i) Storage format for ambiguities
      
    • ii) Treatment of proprietary meta-data regarding genotyping systems
      
    • iii) Bioinformatic approaches for retrospective genotype calls and matching

• 3) Challenges to Consistency in Immunogenomic Data Analysis
  • a) Inconsistent treatment of rare alleles
  • b) Variation in haplotype estimation methods and accuracy of methods
    • i) Limits on number of loci, alleles or sample size
    • ii) Lower bound of sample size to obtain robust estimates
    • iii) Rare haplotypes
    • iv) A priori list of haplotypes (for KIR)
    • v) Impact on calculations of registry donor-pool size
  • c) Hardy-Weinberg testing
    • i) Chi-square testing and rare alleles
    • ii) Exact tests
    • iii) Resampling approaches to approximate exact tests
  • d) Lack of transparency in Donor-Recipient matching algorithms and criteria

• 4) Immunogenomic research needs to be addressed
  • a) Consistent and complementary strategies for data management and analysis
  • b) Ability to synthesize meta-analyses, identify combinable controls, etc.
  • c) Reporting guidelines for immunogenomic studies