Identification of Cell Culture Factors Influencing Afucosylation Levels in Monoclonal Antibodies by Partial Least-Squares Regression and Variable Importance Metrics
afucosylation, cell culture, monoclonal antibodies, partial least-squares regression (PLSR), selectivity ratio (SR), significance multivariate correlation (sMC), variable importance in projection (VIP) scores, variable importance metric
Retrospective analysis of historic data for cell culture processes is a powerful tool to develop further process understanding. In particular, deploying retrospective analyses can identify important cell culture process parameters for controlling critical quality attributes, e.g., afucosylation, for the production of monoclonal antibodies (mAbs). However, a challenge of analyzing large cell culture data is the high correlation between regressors (particularly media composition), which makes traditional analyses, such as analysis of variance and multivariate linear regression, inappropriate. Instead, partial least-squares regression (PLSR) models, in combination with machine learning techniques such as variable importance metrics, are an orthogonal or alternative approach to identifying important regressors and overcoming the challenge of a highly covariant data structure. A specific workflow for the retrospective analysis of cell culture data is proposed that covers data curation, PLS regression, model analysis, and further steps. In this study, the proposed workflow was applied to data from four mAb products in an industrial cell culture process to identify significant process parameters that influence the afucosylation levels. The PLSR workflow successfully identified several significant parameters, such as temperature and media composition, to enhance process understanding of the relationship between cell culture processes and afucosylation levels.
Rish, A., Huang, Z., Siddiquee, K., Xu, J., Anderson, C., Borys, M., & Khetan, A. (2023). Identification of Cell Culture Factors Influencing Afucosylation Levels in Monoclonal Antibodies by Partial Least-Squares Regression and Variable Importance Metrics. Processes, 11 (1). https://doi.org/10.3390/pr11010223