Predicting cell-specific productivity from CHO gene expression

被引：71

作者：

Clarke, Colin ^{[1
]}

Doolan, Padraig ^{[1
]}

Barron, Niall ^{[1
]}

Meleady, Paula ^{[1
]}

O'Sullivan, Finbarr ^{[1
]}

Gammell, Patrick ^{[2
]}

Melville, Mark ^{[3
]}

Leonard, Mark ^{[3
]}

Clynes, Martin ^{[1
]}

机构：

[1] Dublin City Univ, Natl Inst Cellular Biotechnol, Dublin 9, Ireland

[2] Pfizer Inc, BioMfg Sci Grp, Dublin 22, Ireland

[3] Pfizer Inc, Bioproc R&D, Andover, MA 01810 USA

来源：

JOURNAL OF BIOTECHNOLOGY | 2011年 / 151卷 / 02期

基金：

爱尔兰科学基金会;

关键词：

Chinese hamster ovary; Productivity; Microarray; Partial least squares; Cross model validation; Variable selection; PARTIAL LEAST-SQUARES; RECOMBINANT MONOCLONAL-ANTIBODY; CROSS-MODEL VALIDATION; PROBE LEVEL DATA; PROTEOMIC ANALYSIS; MAMMALIAN-CELLS; INFRARED-SPECTROSCOPY; PROTEIN-PRODUCTION; REGRESSION-MODELS; BATCH CULTURE;

D O I：

10.1016/j.jbiotec.2010.11.016

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Improving the rate of recombinant protein production in Chinese hamster ovary (CHO) cells is an important consideration in controlling the cost of biopharmaceuticals. We present the first predictive model of productivity in CHO bioprocess culture based on gene expression profiles. The dataset used to construct the model consisted of transcriptomic data from 70 stationary phase, temperature-shifted CHO production cell line samples, for which the cell-specific productivity had been determined. These samples were utilised to investigate gene expression over a range of high to low monoclonal antibody and fc-fusion-producing CHO cell lines. We utilised a supervised regression algorithm, partial least squares (PLS) incorporating jackknife gene selection, to produce a model of cell-specific productivity (Qp) capable of predicting Qp to within 4.44 pg/cell/day root mean squared error in cross model validation (RMSECMV). The final model, consisting of 287 genes, was capable of accurately predicting Qp in a further panel of 10 additional samples which were incorporated as an independent validation. Several of the genes constituting the model are linked with biological processes relevant to protein metabolism. (C) 2010 Elsevier B.V. All rights reserved.

引用

页码：159 / 165

页数：7