{"entity": "publication", "iuid": "ff620e29e0de4d02ac17b35a7cb3e51f", "timestamp": "2026-11-06T18:28:32.476Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/ff620e29e0de4d02ac17b35a7cb3e51f.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/ff620e29e0de4d02ac17b35a7cb3e51f"}}, "title": "Prediction of drug hypersensitivity by comprehensive modeling of HLA-peptidomes.", "authors": [{"family": "Zhong", "given": "Yi", "initials": "Y", "orcid": "0000-0002-0929-8224", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f5fdb847e9c944d5bba66333c80d40e6.json"}}, {"family": "Lauschke", "given": "Volker M", "initials": "VM", "orcid": "0000-0002-1140-6204", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/82048d4da61547d08aa9d2bb3bae12dd.json"}}, {"family": "Wang", "given": "Yi", "initials": "Y", "orcid": "0000-0002-3676-9183", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a03091d5222a409ba70c5fe26ac5455f.json"}}, {"family": "Zhou", "given": "Yitian", "initials": "Y", "orcid": "0000-0003-3066-5444", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c4e92db79d554ad283927ad7e6e54e8d.json"}}], "type": "journal article", "published": "2026-07-03", "journal": {"title": "Brief. Bioinformatics", "issn": "1477-4054", "volume": "27", "issue": "4", "issn-l": "1467-5463"}, "abstract": "Human leukocyte antigen (HLA)-B*57:01 associated with abacavir-induced hypersensitivity syndrome (ABC-HSS) is one of the most extensively studied immune-mediated drug hypersensitivity reactions (DHRs). The high odds ratio and strong predictive values of HLA-B*57:01 for ABC-HSS have prompted the Food and Drug Administration and European Medicines Agency to require genetic testing before abacavir treatment. Abacavir binds to HLA-B*57:01 and alters the repertoire of presented peptides, resulting in the activation of autoimmunity. Previous studies employing computational approaches to investigate such DHRs have relied solely on a few crystallized tripartite structures, thus overlooking the full presented peptidome, leading to unsatisfactory predictive results. Here, we employed a state-of-the-art modeling approach to generate HLA structures complexed with over 13 000 presented peptides. We then established a novel computational modeling pipeline to simulate the binding of abacavir to these HLA-peptide complexes. Benchmarking against experimentally determined structures showed that this approach successfully recapitulated the crystalized tripartite structures with high accuracy (RMSD<2.2 \u00c5). We then profiled alterations of the peptide repertoire at key positions in the presence of abacavir and proposed a method that accurately predicts compounds known to trigger T-cell activation. Overall, these results show that comprehensive modeling of the HLA-bound peptidome using advanced structural approaches can enhance the prediction and mechanistic understanding of immune-mediated DHRs.", "doi": "10.1093/bib/bbag350", "pmid": "42398070", "labels": {"DDLS Fellow": null, "Yitian Zhou": null}, "xrefs": [{"db": "pmc", "key": "PMC13331351"}, {"db": "pii", "key": "8724529"}], "notes": [], "created": "2026-11-06T09:38:50.984Z", "modified": "2026-11-06T09:38:51.075Z"}