دورية أكاديمية
Separating clinical antibodies from repertoire antibodies, a path to in silico developability assessment
| العنوان: | Separating clinical antibodies from repertoire antibodies, a path to in silico developability assessment |
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| المؤلفون: | Christopher Negron, Joyce Fang, Michael J. McPherson, W. Blaine Stine, Andrew J. McCluskey |
| المصدر: | mAbs, Vol 14, Iss 1 (2022) |
| بيانات النشر: | Taylor & Francis Group, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Therapeutics. Pharmacology LCC:Immunologic diseases. Allergy |
| مصطلحات موضوعية: | Developability, drug discovery, machine learning, repertoire antibodies, therapeutic antibodies, Therapeutics. Pharmacology, RM1-950, Immunologic diseases. Allergy, RC581-607 |
| الوصف: | Approaches for antibody discovery have seen substantial improvement and success in recent years. Yet, advancing antibodies into the clinic remains difficult because therapeutic developability concerns are challenging to predict. We developed a computational model to simplify antibody developability assessment and enable accelerated early-stage screening. To this end, we quantified the ability of hundreds of sequence- and structure-based descriptors to differentiate clinical antibodies that have undergone rigorous screening and characterization for drug-like properties from antibodies in the human repertoire that are not natively paired. This analysis identified 144 descriptors capable of distinguishing clinical from repertoire antibodies. Five descriptors were selected and combined based on performance and orthogonality into a single model referred to as the Therapeutic Antibody Developability Analysis (TA-DA). On a hold-out test set, this tool separated clinical antibodies from repertoire antibodies with an AUC = 0.8, demonstrating the ability to identify developability attributes unique to clinical antibodies. Based on our results, the TA-DA score may serve as an approach for selecting lead antibodies for further development.Abbreviations: Affinity-Capture Self-Interaction Nanoparticle Spectroscopy (AC-SINS), Area Under the Curve (AUC), Complementary-Determining Region (CDR), Clinical-Stage Therapeutics (CST), Framework (FR), Monoclonal Antibodies (mAbs), Observed Antibody Space (OAS), Receiver Operating Characteristic (ROC), Size-Exclusion Chromatography (SEC), Structural Aggregation Propensity (SAP), Therapeutic Antibody Developability Analysis (TA-DA), Therapeutic Antibody Profiler (TAP), Therapeutic Structural Antibody Database (Thera-SAbDab), Variable Heavy (VH), Variable Light (VL). |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 19420862 1942-0870 1942-0862 |
| Relation: | https://doaj.org/toc/1942-0862; https://doaj.org/toc/1942-0870 |
| DOI: | 10.1080/19420862.2022.2080628 |
| URL الوصول: | https://doaj.org/article/e9eca828fb774c6fa14891a2fc97fbaf |
| رقم الأكسشن: | edsdoj.9eca828fb774c6fa14891a2fc97fbaf |
| قاعدة البيانات: | Directory of Open Access Journals |
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Full Text Finder | تدمد: | 19420862 19420870 |
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| DOI: | 10.1080/19420862.2022.2080628 |