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We discussed various synthetic biology strategies to remove pathway bottleneck and how genetically-encoded metabolite sensor could be deployed to improve pathway efficiency.
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The GSEA results were then filtered to identify interesting pathways by 1) removing pathways with <5 clones; 2) removing pathways with >250 clones; 3) removing pathways with FDR q-values>0.05 for the Wilcoxon and LBF tests.
Significantly overlapping pathways were filtered by iteratively going over the list of pathways (sorted by FDR corrected p-value), removing pathways with more than 50% overlap with previous pathways in the list.
Further processing of duplicated data selectively removed pathways whose size deviated from the median, helping to reduce the standard deviation from 23.2 in the original data set to 13.1 in the final data set.
To create a similar database, we downloaded pathways from BioCarta, Pathway Commons, NCBI BioSystems, and WikiPathways, and after removing pathways with no gene members, 2,462 pathways remain (as of February 2012) from specific sources including WikiPathways, Reactome, KEGG, NCI Nature, BioCarta and HumanCyc.
The removal of these reactions would remove any pathway which uses these reactions to balance the metabolite still in the model.
To decrease redundancy, we applied pathway filtering to remove bulky pathways.
While natural systems derive a clear benefit from pathway regulation, past research efforts in engineering cellular metabolism have focused on introducing new pathways and removing existing pathway regulation.
To remove the pathway enzymes that catalyzed the formation of by-products, the three genes encoding a lactate dehydrogenase (ldhA) and two 2,3-butanediol dehydrogenases (budC, and dhaD), respectively, were deleted from the genome.
In contrast, mandatory coverage through public means should mitigate socioeconomic differentials in health as it will remove one pathway where income may impact on health [ 11- 13, 41, 45].
To overcome this problem, metabolic networks can be reduced and simplified using computed fluxes in order to detect and remove insignificant pathways.
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