MAC Lookup fails when it expands to deleted Null allele

[zabeen]

This was observed in AN Atlas Live during import of donors typed with C*06:EDJYM. HLA conversion failed because the allele C*16:199 could not be found.

This name is a truncated version of the full name, C*16:199N which was deleted in the latest IMGT/HLA release (v3.50.0): C*;16:199N;20220630;20220930;06:359N;Name assigned in error.

Investigation shows:

• The full allele name, 16:199N, is present in both the HLA matching and allele names HMD lookup tables of v3.50.0.
• The truncated name is not present in either v3.50.0 table, which is why the lookup failed.
• Both full and truncated names were present in v3.49.0 of the allele names table which is why this error has not occurred previously.

The same issue has been observed with:

• A*;03:200Q;20140623;20170929;03:266N;Sequence error
  • Its full name is stored, but the truncated version (03:200) is not.
• C*;12:274:02N;20191031;20200930;12:329N;Sequence renamed
  • Its full name is stored, but the truncated version (12:274:02) is not.

However, truncated version of these deleted alleles were stored correctly (03:99): C*;03:99:01;20100831;20181026;01:169:01;Sequence renamed C*;03:99:02;20170430;20181026;01:169:02;Sequence renamed There are no other alleles beginning with C*03:99.

Therefore, the cause of the truncated name not being stored in the latest release is because of it being deleted AND it having an expression suffix.

[zabeen]

Testing

• Tested on UAT-ATLAS

Atlas v1.4.1 (pre-release)

• Ran tests on v1.4.1 to ensure the live bug was reproducible in UAT.

Data Refresh

• First ran data refresh to bring instance up to HLA v3.50.0.
  • Total Atlas donor store count of C*06:EDJYM donors: 0
  • HLA expansion failure count reported via alerts: 136
  • HLA expansion failure count reported by AI: 2
  • only logged for Dpb1 84
  • this likely due to AI sampling (see issue #818)

Donor Import

• Imported a donor file copied from live.
  • Atlas donor store count of C*06:EDJYM donors imported from the test file: 171
  • HLA expansion failure count reported via alerts: 172
  • HLA expansion failure count reported by AI specifically for C*06:EDJYM: 113
  • Number of C*06:EDJYM donors in Active matching algorithm db: 0
  • Conclusion: Bug is present on UAT.

Atlas v1.4.2 (post-release)

Donor Import

• Imported a second donor file copied from live; used a different file to ensure donors were imported.

  • Atlas donor store count of C*06:EDJYM donors imported from the test file: 172
  • HLA expansion failure count reported via alerts: 172
  • HLA expansion failure count reported by AI specifically for C*06:EDJYM: 172
  • Number of C*06:EDJYM donors in Active matching algorithm db: 0
  • Conclusion: These failures are expected, as the fix doesn't come into affect until v3.50.0 of the HMD has been rebuilt.

• Forced recreate of v3.50.0 of the HMD via function

• Imported a third donor file copied from live; used a different file to ensure donors were imported.

  • Atlas donor store count of C*06:EDJYM donors imported from the test file: 171
  • HLA expansion failure count reported via alerts: 171
  • HLA expansion failure count reported by AI specifically for C*06:EDJYM: 129 ❌
  • Number of C*06:EDJYM donors in Active matching algorithm db: 0 ❌
  • Conclusion: HLA lookups still failing because HMD caches need to be updated.

• Restarted matching algorithm donor management function to force update of the entire HMD cache.

• Imported a fourth donor file copied from live; used a different file to ensure donors were imported.

  • Atlas donor store count of C*06:EDJYM donors imported from the test file: 190
  • HLA expansion failure count reported via alerts: 0 ✔
  • HLA expansion failure count reported by AI specifically for C*06:EDJYM: 0 ✔
  • Number of C*06:EDJYM donors in Active matching algorithm db: 190 ✔
  • Conclusion: HMD fix has now been fully implemented and has resolved the HLA failures. ✅

Data Refresh

• Re-ran data refresh as a regression test to cover the HLA expansion of lots of different HLA typings.
  • Total Atlas donor store count of C*06:EDJYM donors: 703
  • HLA expansion failure count reported via alerts: 136
  • HLA expansion failure count reported by AI: 136
  • HLA expansion failure count reported by AI specifically for C*06:EDJYM: 0 ✔
  • Number of C*06:EDJYM donors in Active matching algorithm db: 703 ✔
  • Conclusion: The HLA failures reported were the same as those that occurred during data refresh on Atlas v1.4.1. The HMD fix has not introduced any new issues. ✅

Conclusion

• The HMD fix has resolved the described issue and has not introduced any regressions regarding existing HLA lookup functionality. ✅