On this page we will try to explain some behaviour of the match engines in our Search and Match application.
For more info on this please see the following slides.
Table of Contents |
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Antigen Recognition Domain explained
- The antigen recognition domain (ARD) is the binding groove of the HLA peptide. This is the region interacting with the presented antigen and T-cell receptor.
- All alleles that express the same amino acid sequence in this region are considered an allele match.
- The ARD is encoded on:
- exon 2 & 3 for HLA class I
- exon 2 for HLA class II
1. Null allele treatment
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- Null alleles are treated as absent, i.e. the second typing matches as homozygous.
- Null allele matching rules are applied to:
- All high resolution null alleles.
- Null alleles as part of multi allele codes if the null allele is part of a haplotype matching the donor‘s (patient‘s) HLA typing.
- Null allele matching rules are only applied to one typing of the locus.
The following table explains situations where Hap-E performs null allele treatment and whether this is a considered a (potential) match or not.
Patient typing | Donor typing | Hap-E | ATLAS |
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A*03:01, A*01:11N | A*03:01, A*03:01 | matches | matches |
A*03:01, A*01:11N | A*03:01, A*02:125N | matches | matches |
If there is a haplotype compatible with the donor typing containing A*02:125N then | |||
A*03:01, A*01:11N | A*03:01, A*02:GFJM | matches |
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mismatches | ||
A*03:01, A*03:01 | A*03:01, A*02:XX | matches |
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mismatch, but in list as if no mismatch | |||
A*03:01, A*03:01 | A*03:01, A*01:01:01G | does not match | does not match |
A*01:11N, A*02:125N | A*03:01, A*03:01 | does not match | does not match |
02:GFJM ≜ 02:01/02:105/02:125N
2. Search with two mismatches
Hap-E search | ATLAS search |
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The two mismatches can be on any locus. | The two mismatches can be on any locus. |
3. Donors with DNA and serologic typing
Hap-E search | ATLAS search |
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Only the DNA typing information is used for matching. | Only the DNA typing information is used for matching. |
4. Serology handling
Hap-E search | ATLAS search |
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Does not assign expert assigned exceptions described in rel_dna_ser e.g. Hap-E assigns A*;02:55 to A(2) | Does assign expert assigned exceptions described in rel_dna_ser e.g. ATLAS assigns A*;02:55 to A(2) and A(28) |
5. Returning donors without typing at DRB1
Hap-E search | ATLAS search |
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Yes, when default 'return only donors with typing at DRB1' filter has been switched off and donor does have typing at A+B and at least 1 of: C, DQB1 loci. | No, because donors without typing at DRB1 are not accepted by ATLAS as valid donors. |
6. Match grades: Overview
Standard match grades |
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Applied to locus A, B, C, DRB1, DQB1 |
7. DPB1-specific match grades
Hap-E search | ATLAS search |
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Applied to DPB1 only. Uses TCE3 model |
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5. No haplotype based probability available
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Applied to DPB1 only. Uses TCE3 model | |
Ambiguous typing can be determined. For an ambiguous case (i.e. depending on the realization of a multi allele code on DPB1 of patient or donor, the mismatch can be P, H or G) the probabilities are calculated based on DPB1 allele frequencies and are displayed when hovering over the displayed DPB1 match-grade icon of the donor or CBU: | Ambiguous typing can't be determined. Ambiguous typing is displayed as "-" (Unknown) |
8. Handling of HLA*DRB3, DRB4, DRB5, DQA1 and other loci not considered for overall match probability
Hap-E search | ATLAS search |
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HLA*DRB3/4/5, DPA1, DQA1 and E are validated and shown in the full report, including information whether they are matched or not. | Loci other than A, B, C, DRB1, DQB1 and DPB1 are not validated or imported by ATLAS and therefore also not returned. |
9. Handling of 'NEW' alleles
Handling of new alleles that do not have an official name yet.
For guidelines regarding implementation and reporting of 'NEW' alleles, please read https://onlinelibrary.wiley.com/doi/10.1111/tan.15048
Hap-E search | ATLAS search |
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No probabilities are calculated (inexplicable donor).
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No probabilities are calculated (inexplicable donor).
Supported for Donors and Patients. However, Search & Match including Dataupload currently only supports NEW alleles for Patients. Therefore only NEW alleles for patients will be processed in Search & Match. | Currently not supported. |
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. Cord Blood search options
Hap-E search | ATLAS search |
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Allele matched:
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| Allele matched:
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- n/6 search at HLA-A, B, DRB1
11. 3 and 4 mismatch Cord Blood sorting
Hap-E search | ATLAS search |
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Resolution based scoring CBUs with high resolution typing are ranked higher than less well typed CBUs in the 3 and 4 mismatch category. e.g. DNA typed CBUs are ranked higher than serology typed CBUs | Match confidence based scoring CBUs with a higher match confidence are ranked higher than CBUs with a lower match confidence in the 3 and 4 mismatch category. e.g. CBUs with exact matches at considered loci are ranked higher than those with possible matches at considered loci. |
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. Probability display
Hap-E search | ATLAS search |
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All probabilities are rounded to integer values. → 0%:
| All probabilities are rounded to integer values. → 0%:
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13.1 Locus match probabilities: Definition
Hap-E search | ATLAS search |
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match, i.e. 10/10, 8/8 or 6/6
mismatch, i.e. 9/10, 7/8 or 5/6
So this probability provides information on which locus the next mismatch will occur. | match, i.e. 10/10, 8/8 or 6/6
mismatch, i.e. 9/10, 7/8 or 5/6
So this probability provides information on the probability that this locus will be a match |
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13.2 Locus match probabilities in
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search: Not displayed
In some cases the value is not defined and no locus match probability is displayed:
Hap-E search | ATLAS search |
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match
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| match |
- When p1 = 0 (division by zero, not defined).
mismatch
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mismatch
inexplicable donors
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13.3 Locus match probabilities in Hap-E and ATLAS search
Example 1:
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8.3 Locus match probabilities in Hap-E search: Example 2
8.3 Locus match probabilities in Hap-E search: Example 3
8.3 Locus match probabilities in Hap-E search: Example 4
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