Statistical characterization of therapeutic protein modifications
| العنوان: | Statistical characterization of therapeutic protein modifications |
|---|---|
| المؤلفون: | William E Haskins, Olga Vitek, Fred Jacobson, Qiuting Hong, Gregory A. Ryslik, Chen Yan, Theo Koulis, Zhiqi Hao, Benjamin Moore, Cinzia Stella, Michael Kim, Tsung-Heng Tsai, Erik Verschueren, Jeffrey H. Zhang |
| المصدر: | Scientific Reports Scientific Reports, Vol 7, Iss 1, Pp 1-13 (2017) |
| بيانات النشر: | Nature Publishing Group UK, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, medicine.drug_class, Computer science, Science, Computational biology, Biostatistics, Monoclonal antibody, Mass spectrometry, Tandem mass spectrometry, 01 natural sciences, Peptide Mapping, Article, 03 medical and health sciences, Tandem Mass Spectrometry, medicine, Technology, Pharmaceutical, Simulation, Chromatography, High Pressure Liquid, Biological Products, Multidisciplinary, Peptide mapping, 010401 analytical chemistry, Therapeutic protein, Proteins, Statistical model, 0104 chemical sciences, Characterization (materials science), 030104 developmental biology, Medicine, Protein Processing, Post-Translational |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 2045-2322 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5440a1281217169632d9cdfd807efd81 http://europepmc.org/articles/PMC5554216 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....5440a1281217169632d9cdfd807efd81 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
|---|