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Title: Computing optimal factories in metabolic networks with negative regulation
Abstract Motivation

A factory in a metabolic network specifies how to produce target molecules from source compounds through biochemical reactions, properly accounting for reaction stoichiometry to conserve or not deplete intermediate metabolites. While finding factories is a fundamental problem in systems biology, available methods do not consider the number of reactions used, nor address negative regulation.

Methods

We introduce the new problem of finding optimal factories that use the fewest reactions, for the first time incorporating both first- and second-order negative regulation. We model this problem with directed hypergraphs, prove it is NP-complete, solve it via mixed-integer linear programming, and accommodate second-order negative regulation by an iterative approach that generates next-best factories.

Results

This optimization-based approach is remarkably fast in practice, typically finding optimal factories in a few seconds, even for metabolic networks involving tens of thousands of reactions and metabolites, as demonstrated through comprehensive experiments across all instances from standard reaction databases.

Availability and implementation

Source code for an implementation of our new method for optimal factories with negative regulation in a new tool called Odinn, together with all datasets, is available free for non-commercial use at http://odinn.cs.arizona.edu.

 
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Award ID(s):
2041613
NSF-PAR ID:
10406871
Author(s) / Creator(s):
;
Publisher / Repository:
Oxford University Press
Date Published:
Journal Name:
Bioinformatics
Volume:
38
Issue:
Supplement_1
ISSN:
1367-4803
Format(s):
Medium: X Size: p. i369-i377
Size(s):
["p. i369-i377"]
Sponsoring Org:
National Science Foundation
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