Identification of Cell Culture Factors Influencing Afucosylation Levels in Monoclonal Antibodies by Partial Least-Squares Regression and Variable Importance Metrics

Rish, Adam J.; Huang, Zhuangrong; Siddiquee, Khandaker; Xu, Jinying; Anderson, Carl A.; Borys, Michael; Khetan, Anurag

doi:10.3390/pr11010223

Cited by 4 publications

(3 citation statements)

References 35 publications

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“…Partial Least Squares (PLS) analysis is employed in conducting multivariate analysis to investigate the correlation between independent and dependent variables in research (Rish et al 2023). PLS offers a distinct advantage in addressing the challenges associated with intricate interrelationships among variables and can effectively establish connections by incorporating additional variables as mediators (Sarstedt et al 2020).…”

Section: Partial Least Squares (Pls) Algorithm Test Resultsmentioning

confidence: 99%

Fostering Community Participation: The Role of Forestry Extension Officers in Maximizing Social Capital for National Park Conservation

Suswadi,

Irawan,

Esthi

2023

J. Sylva Lestari

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The lack of community involvement poses a significant obstacle that may impede the achievement of success in the conservation partnership program between the Mount Merbabu National Park (MMNP) authority and the local community. This study serves a purpose and presents a new approach by investigating the impact of human and social capital on community engagement in the conservation partnership program, with the mediation of the extension worker’s role. This location was determined using a purposive method, focusing primarily on three villages surrounding MMNP, Indonesia. The sampling technique employed was simple random sampling, where 30 respondents were chosen from each village, resulting in a total sample size of 90 respondents. This study examines the variables using the Structural Equation Model (SEM) - Partial Least Squares (PLS) approach. Social capital has a positive and significant impact on community engagement through forestry extension workers, while human capital does not affect community conservation partnership involvement through the same workers. This study recommends enhancing social capital to increase community participation in conservation initiatives. Forestry extension officers should improve communication, social networks, and environmental competency to encourage greater community involvement in environmental protection. Keywords: community engagement, extension workers role, forest conservation, human capital, social capital

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Section: Partial Least Squares (Pls) Algorithm Test Resultsmentioning

confidence: 99%

Fostering Community Participation: The Role of Forestry Extension Officers in Maximizing Social Capital for National Park Conservation

Suswadi,

Irawan,

Esthi

2023

J. Sylva Lestari

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“…Empirical statistical models and machine learning techniques can capture trends on and generate predictions from the relationships between influential factors and afucosylation levels. [54,76,77] Mechanistic models link the observed data directly to the underlying cellular metabolism. The dynamic metabolism of mammalian cells is best described according to kinetic models.…”

Section: Perspective Workflow For Understanding and Controlling Afuco...mentioning

confidence: 99%

Strategies for controlling afucosylation in monoclonal antibodies during upstream manufacturing

Rish

Siddiquee

Huang

et al. 2023

Biotechnology Journal

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Core fucosylation is a highly prevalent and significant feature of N-glycosylation in therapeutic monoclonal antibodies produced by mammalian cells where its absence (afucosylation) plays a key role in treatment safety and efficacy. Notably, even slight changes in the level of afucosylation can have a considerable impact on the antibody-dependent cell-mediated cytotoxicity. Therefore, implementing control over afucosylation levels is important in upstream manufacturing to maintain consistent quality across batches of product, since standard downstream processing does not change afucosylation. In this review, the influences and strategies to control afucosylation are presented. In particular, there is emphasis on upstream manufacturing culture parameters and media supplementation, as these offer particular advantages as control strategies over alternative approaches such as cell line engineering and chemical inhibitors. The review discusses the relationship between the afucosylation influences and the underlying cellular metabolism to promote increased process understanding. Also, briefly highlighted is the value of empirical and mechanistic models in evaluating and designing control methods for core fucosylation.

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“…Glycosylation has been modeled in detail, allowing a better understanding of glycoform biosynthesis. [ 7–9 ] However, the amount of prior knowledge and the need to create new knowledge for more complex drug targets strongly limits this approach.…”

Section: Introductionmentioning

confidence: 99%

An innovative hybrid modeling approach for simultaneous prediction of cell culture process dynamics and product quality

Polak,

Huang,

Sokolov

et al. 2024

Biotechnology Journal

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The use of hybrid models is extensively described in the literature to predict the process evolution in cell cultures. These models combine mechanistic and machine learning methods, allowing the prediction of complex process behavior, in the presence of many process variables, without the need to collect a large amount of data. Hybrid models cannot be directly used to predict final product critical quality attributes, or CQAs, because they are usually measured only at the end of the process, and more mechanistic knowledge is needed for many classes of CQAs. The historical models can instead predict the CQAs better; however, they cannot directly relate manipulated process parameters to final CQAs, as they require knowledge of the process evolution. In this work, we propose an innovative modeling approach based on combining a hybrid propagation model with a historical data‐driven model, that is, the combined hybrid model, for simultaneous prediction of full process dynamics and CQAs. The performance of the combined hybrid model was evaluated on an industrial dataset and compared to classical black‐box models, which directly relate manipulated process parameters to CQAs. The proposed combined hybrid model outperforms the black‐box model by 33% on average in predicting the CQAs while requiring only around half of the data for model training to match performance. Thus, in terms of model accuracy and experimental costs, the combined hybrid model in this study provides a promising platform for process optimization applications.

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Identification of Cell Culture Factors Influencing Afucosylation Levels in Monoclonal Antibodies by Partial Least-Squares Regression and Variable Importance Metrics

Cited by 4 publications

References 35 publications

Fostering Community Participation: The Role of Forestry Extension Officers in Maximizing Social Capital for National Park Conservation

Fostering Community Participation: The Role of Forestry Extension Officers in Maximizing Social Capital for National Park Conservation

Strategies for controlling afucosylation in monoclonal antibodies during upstream manufacturing

An innovative hybrid modeling approach for simultaneous prediction of cell culture process dynamics and product quality

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