Challenges and future directions of AIRR-seq-based diagnostics

Adaptive Immune Receptor Repertoire sequencing (AIRR-seq) is a promising diagnostic method across various clinical conditions, yet its widespread implementation faces several challenges. This perspective examines the current landscape of AIRR-seq diagnostics and outlines key obstacles and opportunit...

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Main Authors: Ulrik Stervbo, Paraskevas Filippidis, Felix Breden, Lindsay G. Cowell, Frederic Davi, Victor Greiff, Anton W. Langerak, Eline T. Luning Prak, Alexandra F. Sharland, Enkelejda Miho, Pieter Meysman
Format: Article
Language:English
Published: Elsevier 2025-09-01
Series:ImmunoInformatics
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Online Access:http://www.sciencedirect.com/science/article/pii/S2667119025000096
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author Ulrik Stervbo
Paraskevas Filippidis
Felix Breden
Lindsay G. Cowell
Frederic Davi
Victor Greiff
Anton W. Langerak
Eline T. Luning Prak
Alexandra F. Sharland
Enkelejda Miho
Pieter Meysman
author_facet Ulrik Stervbo
Paraskevas Filippidis
Felix Breden
Lindsay G. Cowell
Frederic Davi
Victor Greiff
Anton W. Langerak
Eline T. Luning Prak
Alexandra F. Sharland
Enkelejda Miho
Pieter Meysman
author_sort Ulrik Stervbo
collection DOAJ
description Adaptive Immune Receptor Repertoire sequencing (AIRR-seq) is a promising diagnostic method across various clinical conditions, yet its widespread implementation faces several challenges. This perspective examines the current landscape of AIRR-seq diagnostics and outlines key obstacles and opportunities for advancement. Critical challenges include the need for standardized quality controls, privacy protection under General Data Protection Regulation (GDPR) and Health Insurance Portability and Accountability Act (HIPAA) frameworks, and the development of clinically compatible bioinformatics pipelines. Machine learning approaches offer potential solutions for interpreting complex repertoire signatures, though these models must balance accuracy with interpretability for clinical adoption. Future applications may include early disease detection, prognosis, and monitoring of treatment and vaccine responses. However, successful clinical integration will require sustained collaboration among funding bodies, regulatory agencies, researchers, diagnosticians, and clinicians to establish clear guidelines and expand existing repositories with well-characterized patient samples. The collaborative efforts of the AIRR Diagnostics Working Group and the AIRR Community's initiatives are working towards unlocking the potential of AIRR-seq in precision medicine and enhancing diagnostic capabilities.
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spelling doaj-art-d5ebc63ef4414bcb8edc426f65650fb12025-08-20T03:56:17ZengElsevierImmunoInformatics2667-11902025-09-011910005610.1016/j.immuno.2025.100056Challenges and future directions of AIRR-seq-based diagnosticsUlrik Stervbo0Paraskevas Filippidis1Felix Breden2Lindsay G. Cowell3Frederic Davi4Victor Greiff5Anton W. Langerak6Eline T. Luning Prak7Alexandra F. Sharland8Enkelejda Miho9Pieter Meysman10Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Herne, Germany; Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin-Brandenburg Center for Regenerative Therapies, Augustenburger Platz 1, 13353 Berlin, Germany; Corresponding author.Department of Pathology, Yale School of Medicine, New Haven, 06511, CT, USADepartment of Biological Sciences, Simon Fraser University, Burnaby, BC V5A 1S6, CanadaDepartment of Health Data Science and Biostatistics, O’Donnell School of Public Health and Department of Immunology, School of Biomedical Sciences, UT Southwestern Medical Center, Dallas, TX, 75390, USALaboratory of Molecular Hematology, Department of Hematology, Hôpital Pitié-Salpêtrière, APHP, Sorbonne Université, Paris, FranceDepartment of Immunology, University of Oslo and Oslo University Hospital, Oslo, Norway; Imprint Labs, LLC, NY, NY, USALaboratory Medical Immunology, Department Immunology, Erasmus MC, University Medical Center, Rotterdam, the NetherlandsDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, Philadelphia, PA 19104, USASydney Medical School, Faculty of Medicine and Health, University of Sydney, NSW 2006, AustraliaInstitute of Medical Engineering and Medical Informatics, School of Life Sciences, University of Applied University of Sciences and Arts Northwestern Switzerland, Muttenz, Switzerland; aiNET GmbH, Basel, Switzerland; Swiss Bioinformatics Institute, Lausanne, SwitzerlandAntwerp Unit for Data Analysis and Computation in Immunology and Sequencing, University of Antwerp, Antwerp, BelgiumAdaptive Immune Receptor Repertoire sequencing (AIRR-seq) is a promising diagnostic method across various clinical conditions, yet its widespread implementation faces several challenges. This perspective examines the current landscape of AIRR-seq diagnostics and outlines key obstacles and opportunities for advancement. Critical challenges include the need for standardized quality controls, privacy protection under General Data Protection Regulation (GDPR) and Health Insurance Portability and Accountability Act (HIPAA) frameworks, and the development of clinically compatible bioinformatics pipelines. Machine learning approaches offer potential solutions for interpreting complex repertoire signatures, though these models must balance accuracy with interpretability for clinical adoption. Future applications may include early disease detection, prognosis, and monitoring of treatment and vaccine responses. However, successful clinical integration will require sustained collaboration among funding bodies, regulatory agencies, researchers, diagnosticians, and clinicians to establish clear guidelines and expand existing repositories with well-characterized patient samples. The collaborative efforts of the AIRR Diagnostics Working Group and the AIRR Community's initiatives are working towards unlocking the potential of AIRR-seq in precision medicine and enhancing diagnostic capabilities.http://www.sciencedirect.com/science/article/pii/S2667119025000096AIRR-seqDiagnosticsStandardizationClinical translationMachine learningInterpretability
spellingShingle Ulrik Stervbo
Paraskevas Filippidis
Felix Breden
Lindsay G. Cowell
Frederic Davi
Victor Greiff
Anton W. Langerak
Eline T. Luning Prak
Alexandra F. Sharland
Enkelejda Miho
Pieter Meysman
Challenges and future directions of AIRR-seq-based diagnostics
ImmunoInformatics
AIRR-seq
Diagnostics
Standardization
Clinical translation
Machine learning
Interpretability
title Challenges and future directions of AIRR-seq-based diagnostics
title_full Challenges and future directions of AIRR-seq-based diagnostics
title_fullStr Challenges and future directions of AIRR-seq-based diagnostics
title_full_unstemmed Challenges and future directions of AIRR-seq-based diagnostics
title_short Challenges and future directions of AIRR-seq-based diagnostics
title_sort challenges and future directions of airr seq based diagnostics
topic AIRR-seq
Diagnostics
Standardization
Clinical translation
Machine learning
Interpretability
url http://www.sciencedirect.com/science/article/pii/S2667119025000096
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