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We provide a step-by-step guidance with example dataset to navigate through the webserver and explore the possible outputs. The example samples are VEP-annotated VCF files publicly available from the GIAB consortium.

Primary output

  • Allogenomic Mismatch Score (AMS):

    The AMS is the computation of the directional amino acid mismatches as an approach of the minor histocompatibility antigens load. The higher the AMS, the higher the expected alloreactivity after transplantation.

    The distribution of AMS values across our cohorts is given for contextual score interpretation, but keep in mind that the AMS depends on the quality thresholds applied for the computation.

    If you are working from a joint VCF, you will get additional informations on the quality of the sequencing of your pair that are:
    • The ref/ratio: The higher the ref/ratio, the higher the quality of the sequencing for the pair.
    • The normalized AMS: Relying on the ref/ratio, normalized AMS makes the comparison of AMS more robust across one cohort by taking into account the quality of the sequencing of each pair.
  • Mismatches table:
    In this table, you will find informations on the mismatched amino acids contributing to the AMS.

    In case you toggled the imputation, some lines are empty for either the donor or the recipient. It is the normal behaviour of the computation with imputation, meant to impute that any missing information for either the donor or the recipient is a ref/ref position (GT = 0/0).

  • Transcripts table:
    This table is primary generated to compute the peptides, but will give you more insights on the transcripts expected to be generated from the mismatches table.

  • D0/R0 tables:
    Those tables (D0 for the one sample you designated as the donor, R0 for the recipient) contain basic informations extracted from the VCF files then used to compute the score.

Post processing

The postprocess of your data will return you the following files

  • Filtered mismatches table:
    After the computation of AMS, you can postprocess your primary outputs to restrict the mismatches tables to some genomic regions, rsID, genes or transcript of interest.

  • Peptides list:
    The tool will generate a list of peptides of the requested length from the mismatches table filtered or not.
    This list can be processed by third-party tools to assess their affinity towards HLA molecules, which refines the minor histocompatibility antigens.