Preprint Article Version 1 This version is not peer-reviewed

Assessing and Resolving Model Misspecifications in Metabolic Flux Analysis

Version 1 : Received: 16 March 2017 / Approved: 16 March 2017 / Online: 16 March 2017 (17:38:36 CET)

A peer-reviewed article of this Preprint also exists.

Gunawan, R.; Hutter, S. Assessing and Resolving Model Misspecifications in Metabolic Flux Analysis. Bioengineering 2017, 4, 48. Gunawan, R.; Hutter, S. Assessing and Resolving Model Misspecifications in Metabolic Flux Analysis. Bioengineering 2017, 4, 48.

Journal reference: Bioengineering 2017, 4, 48
DOI: 10.3390/bioengineering4020048

Abstract

Background: Metabolic flux analysis (MFA) is an indispensable tool in metabolic engineering. The simplest variant of MFA relies on an overdetermined stoichiometric model of the cell’s metabolism under the pseudo-steady state assumption, to evaluate the intracellular flux distribution. Despite its long history, the issue of model error in the overdetermined MFA, particularly misspecifications of the stoichiometric matrix, has not received much attention. Method: We evaluated the performance of statistical tests from linear least square regressions, namely Ramsey RESET test, F-test and Lagrange multiplier test, in detecting model misspecifications in the overdetermined MFA, particularly missing reactions. We further proposed an iterative procedure using the F-test to correct such an issue. Result: Using Chinese hamster ovary and random metabolic networks, we demonstrated that: (1) a statistically significant regression does not guarantee high accuracy of the flux estimates, (2) the removal of a reaction with a low flux magnitude can cause disproportionately large biases in the flux estimates, (3) the F-test could efficiently detect missing reactions, and (4) the proposed iterative procedure could robustly resolve the omission of reactions. Conclusion: Our work demonstrated that statistical analysis and tests could be used to systematically assess, detect and resolve model misspecifications in the overdetermined MFA.

Subject Areas

metabolic flux analysis, model misspecification, constraint-based model, stoichiometric model, Chinese hamster ovary cell culture

Readers' Comments and Ratings (0)

Leave a public comment
Send a private comment to the author(s)
Rate this article
Views 0
Downloads 0
Comments 0
Metrics 0
Leave a public comment

×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.