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Statistical characterization of therapeutic protein modifications

التفاصيل البيبلوغرافية
العنوان: Statistical characterization of therapeutic protein modifications
المؤلفون: Tsung-Heng Tsai, Zhiqi Hao, Qiuting Hong, Benjamin Moore, Cinzia Stella, Jeffrey H. Zhang, Yan Chen, Michael Kim, Theo Koulis, Gregory A. Ryslik, Erik Verschueren, Fred Jacobson, William E. Haskins, Olga Vitek
المصدر: Scientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
بيانات النشر: Nature Portfolio, 2017.
سنة النشر: 2017
المجموعة: LCC:Medicine
LCC:Science
مصطلحات موضوعية: Medicine, Science
الوصف: Abstract Peptide mapping with liquid chromatography–tandem mass spectrometry (LC-MS/MS) is an important analytical method for characterization of post-translational and chemical modifications in therapeutic proteins. Despite its importance, there is currently no consensus on the statistical analysis of the resulting data. In this manuscript, we distinguish three statistical goals for therapeutic protein characterization: (1) estimation of site occupancy of modifications in one condition, (2) detection of differential site occupancy between conditions, and (3) estimation of combined site occupancy across multiple modification sites. We propose an approach, which addresses these goals in terms of summarizing the quantitative information from the mass spectra, statistical modeling, and model-based analysis of LC-MS/MS data. We illustrate the approach using an LC-MS/MS experiment from an antibody-drug conjugate and its monoclonal antibody intermediate. The performance was compared to a ‘naïve’ data analysis approach, by using computer simulation, evaluation of differential site occupancy in positive and negative controls, and comparisons of estimated site occupancy with orthogonal experimental measurements of N-linked glycoforms and total oxidation. The results demonstrated the importance of replicated studies of protein characterization, and of appropriate statistical modeling, for reproducible, accurate and efficient site occupancy estimation and differential analysis.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2045-2322
Relation: https://doaj.org/toc/2045-2322
DOI: 10.1038/s41598-017-08333-y
URL الوصول: https://doaj.org/article/08510379a20f40e192b97fe2f553e394
رقم الأكسشن: edsdoj.08510379a20f40e192b97fe2f553e394
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:20452322
DOI:10.1038/s41598-017-08333-y