Glycosylation is a topic of intense current interest in the development of biopharmaceuticals because it is related to drug safety and efficacy. This work describes results of an interlaboratory study on the glycosylation of the Primary Sample (PS) of NISTmAb, a monoclonal antibody reference material. Seventy-six laboratories from industry, university, research, government, and hospital sectors in Europe, North America, Asia, and Australia submitted a total of 103 reports on glycan distributions. The principal objective of this study was to report and compare results for the full range of analytical methods presently used in the glycosylation analysis of mAbs. Therefore, participation was unrestricted, with laboratories choosing their own measurement techniques. Protein glycosylation was determined in various ways, including at the level of intact mAb, protein fragments, glycopeptides, or released glycans, using a wide variety of methods for derivatization, separation, identification, and quantification. Consequently, the diversity of results was enormous, with the number of glycan compositions identified by each laboratory ranging from 4 to 48. In total, one hundred sixteen glycan compositions were reported, of which 57 compositions could be assigned consensus abundance values. These consensus medians provide community-derived values for NISTmAb PS. Agreement with the consensus medians did not depend on the specific method or laboratory type. The study provides a view of the current state-of-the-art for biologic glycosylation measurement and suggests a clear need for harmonization of glycosylation analysis methods.
Various investigators have proposed that "scientific geniuses" are polymaths. To test this hypothesis, autobiographies, biographies, and obituary notices of Nobel Prize winners in the sciences, members of the Royal Society, and the U.S. National Academy of Sciences were read and adult arts and crafts avocations tabulated. Data were compared with a 1936 avocation survey of Sigma Xi members and a 1982 survey of arts avocations among the U.S. public. Nobel laureates were significantly more likely to engage in arts and crafts avocations than Royal Society and National Academy of Sciences members, who were in turn significantly more likely than Sigma Xi members and the U.S. public. Scientists and their biographers often commented on the utility of their avocations as stimuli for their science. The utility of arts and crafts training for scientists may have important public policy and educational implications in light of the marginalization of these subjects in most curricula.
Glyco-Mapper is a novel systems biology product quality prediction tool created using a new framework termed: Discretized Reaction Network Modeling using Fuzzy Parameters (DReaM-zyP). Within Glyco-Mapper, users fix the nutrient feed composition and the glycosylation reaction fluxes to fit the model glycoform to the reference experimental glycoform, enabling cell-line specific glycoform predictions as a result of cell engineering strategies. Glyco-Mapper accurately predicts glycoforms associated with genetic alterations that result in the appearance or disappearance of one or more glycans with an accuracy, sensitivity, and specificity of 96%, 85%, and 97%, respectively, for publications between 1999 and 2014. The modeled glycoforms span a large range of glycoform engineering strategies, including the altered expression of glycosylation, nucleotide sugar transport, and metabolism genes, as well as an altered nutrient feeding strategy. A glycoprotein-producing CHO cell line reference glycoform was modeled and a novel Glyco-Mapper prediction was experimentally confirmed with an accuracy and specificity of 95% and 98%, respectively. Glyco-Mapper is a product quality prediction tool that provides a streamlined way to design host cell line genomes to achieve specific product quality attributes.
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