With the last release of our the Search & Match Service, the WMDA has maintained a similar haplotype frequency set configuration as was used in Optimatch (Search & Match v1). The Search & Match Service currently contains no ethnicity information for donors and therefore the new frequency sets will be calculated and based upon geographical and available data of the donors of an organisation. These frequency sets utilize high resolution typing results from In most cases the ION of the donor/ cord blood unit will determine which haplotype frequency set is used.
To provide a more up-to-date representation of the donor pools world wide, the haplotype frequency set calculations have been performed using the latest data in the WMDA Donor and CBU database. Calcations were performed using the open source algorithm Haplo-o-Mat (https://github.com/DKMS/Hapl-o-Mat and https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5450239/) using high resolution typing results from organisations to extrapolate the haplotypes of the region or organisation. Thus, an organisation or geographical region must meet a minimum threshold of number of donors and availability of high resolution typing to build usable and valuable frequencies. For cord blood units. we will use the same sets that were determined in the donor populations.
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5-locus Haplofrequency estimation was performed on all organisations/populations with at least 5000 10000 donors in HLA-A, -B, -C, -DRB1 and -DRB1 types in 90% high resolutionDQB1 types where ambiguity was low enough to be useful. Organisations in the same country/within the same population are usually combined, e.g. AT-ABMDR (Austrian Bone Marrow Donors) and AT-Verein (Austria- Verein geben fur Lebel) but *not* for US-NMDP (general US population) and US-GOL (predominantly Ashkenazi Jews). The 90% criteria is based on the global frequency set and includes all allele codes whose top 90% cumulated allele frequencies are in high resolution.
The current global frequency set will continue to currently be used for donors of organisations if it is the best representationall patients and for donors that for some reason do not match a typical haplotype frequency set. For example when a registry is new and has not yet been assigned to an appropriate existing haplotype frequency set or when the HLA typings from this registry deviate substantially enough from any typical haplotype frequency set that it does not make sense to assign them to one. The number of this frequency set is 999. We currently return the haplotype frequency set in the search results API endpoint for CBUs and will soon add it for donors.
Below, you can find a figure how the haplotype frequency (HF) sets are assigned to the donors and cord blood units. The system first determines if both COUNTRY and ETHNICITY are provided. If yes, then it will check if an ethnicity specific set for this country exists. If the donor for example is coming from USA and has ethnicity HISA, then we do not have a specific set available. However, there is a more broad Hispanic HF set available (USA-HI) and this will then be used.
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