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Published on: December 7, 2021
HLAnte: A Python command-line interface for unified HLA genotype annotation with integrated pharmacogenomic, disease,
1Department of Biology, Graduate School of Natural and Applied Sciences, Ankara University, Şehit Ömer Halisdemir Boulevard, 06110 Dışkapı, Ankara, Turkey; Intergen Genetics and Rare Diseases Diagnosis Research and Application Center, 2119th Street, Mustafa Kemal District, 06510 Çankaya, Ankara, Turkey.
Abstract:
The human leukocyte antigen (HLA) system is the most polymorphic gene complex in the human genome and plays a central role in susceptibility to autoimmune disease and drug hypersensitivity. HLA typing tools arcasHLA, T1K, HLA-HD and OptiType each emit a distinct output, creating a manual reformatting bottleneck. We present HLAnte, a Python command-line interface that parses all four formats, normalizes calls against a version-pinned IPD-IMGT/HLA database, and consolidates GWAS Catalog, PharmGKB, Clinical Pharmacogenetics Implementation Consortium (CPIC), and Allele Frequency Net Database (AFND) evidence in one provenance-tagged report. Across 2692 samples from the 1000 Genomes Project, parse rates were 99.8-99.9% and HLAnte matched 26,300 of 26,301 calls to an IPD-IMGT/HLA name; that is coverage, not specificity: only 0.75% of calls resolve to a single allele. We quantified annotation-retrieval fidelity, not clinical detection: CPIC Level 1A retrieval was 100% for four sentinel allele-drug pairs and disease-annotation retrieval 99.7-100% across seven allele-disease pairs. AFND coverage (the proportion of annotated calls with a population allele-frequency record for the sample's super-population) was 99.8-100% in every super-population with the full AFND snapshot. Three worked examples illustrate use: pharmacogenomic triage, population-referenced frequency reporting, and cohort disease-association screening. HLAnte is available under the MIT license (https://github.com/efe3506/HLAnte).
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