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Flow restoration to all 95 metabolites was attempted using GapFill by adding reactions from KEGG [ 44].
Gap-filling (Kumar et al., 2007; Orth and Palsson, 2010; Reed et al., 2006) is the process of completing the reaction network of an organism, by adding reactions from a reference DB, to produce a set of biomass metabolites.
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In the latter category, the GapFill method was specifically developed to identify dead-ends in models, and correct them by adding reaction from a global repository of reactions, changing the reversibility status of reactions, or adding transporters (Kumar et al., 2007).
Then, we progressively increase the number of seeds by adding reactions randomly selected from the reference pathway, and re-do the inference and evaluation, until all reactions of the pathway are selected as seeds.
One can reach G2 from G1 by adding reaction R4 and removing R1, an event that we refer to as a reaction swap [ 10, 12, 33].
(Adds reactions from China, South Korea in paragraphs 3, 12-13).
(Adds reaction from candidates).
(Adds reaction from Canadian government).
(Adds reaction from TV star and others).
Gap analysis was also conducted and gaps were reduced by adding essential reactions from KEGG and other databases.
In general, such a completion might be infeasible (meaning the linear optimizer still finds no solution even after gap-filling) since some biomass metabolites might not be producible even by adding all reactions from the reference DB.
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