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Sadd et al. [ 31] also enumerated pathway component expression in workers, but we identified more complete coverage of expected pathways, including a complete Toll signalling pathway.
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Finally, RetroPath2.0 was originally developed to enumerate pathways producing a given target product from a source set of reactants.
The work most closely related to ours is [23], which models metabolic pathways as a type of hyperpaths and gives a method for enumerating pathways between a set of source compounds and a target compound in the network.
Traditional systems of medicine are less about enumerating pathways and specifying mechanisms than they are about pattern recognition and the application of metaphor.
The algorithm given below enables one to detect bootstraps prior enumerating pathways running the FindPath algorithm.
Unfortunately, the algorithms proposed in [ 21], do not enumerate pathways and are therefore not directly applicable to our metabolic engineering problem.
In the context of metabolic engineering (i.e. enumerating pathways between native metabolites and heterologous targets) we found only few inconsistent pathways (less than 1% of the 23564 enumerated pathways).
Prior to enumerating pathways with elementary modes, extreme pathways or the direct algorithm, bootstraps were identified by using the algorithm FindBootstraps defined in Methods and added to the growth media.
Since FindPath algorithm has been designed with the aim to enumerate pathways in metabolic engineering applications, it does not directly address other general metabolic network analysis problems like finding shortest paths between two compounds of endogenous pathways in central metabolisms.
Indeed, FindPath does not enumerate pathways comprising compounds (bootstraps) that are consumed before being produced unless they were added as supplement in the growth medium (cf. in Additional file 3 an example of pathway enumeration with FindPath using bootstrap compounds).
While as mentioned above, the problem of systematically enumerating pathways for heterologous production in chassis organisms has not yet been addressed, there are methods based on the steady state approach to search for heterologous pathways optimizing target productions [ 9], and methods to search for shortest pathways between source and target sets of compounds [ 10] and [ 11].
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