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In order to identify those metabolic reactions obeying low flux variability and high essentiality we selected two threshold values.
Given that the definition of gene essentiality in vitro depends on the threshold selected for cell death (namely the mean cell number reduction in the ccRCC screen and the caspase activity z-score in the PC screen), we performed a sensitivity analysis on these thresholds for all tested scenarios (implemented constraints, cancer types, and medium definition).
The sensitivity and specificity of the iNJ661v network model were substantially larger than those of the other two networks regardless of the threshold used to determine essentiality.
The calculated sensitivity, specificity, and MCCs depend on the value chosen for the growth rate ratio threshold to determine gene essentiality.
Varying the threshold of importance values that corresponds to essentiality gives a series of sensitivity and specificity values that form an ROC curve.
The sensitivity for the predicted essentiality of these networks ranged from 0.23 to 0.44 depending on the threshold used.
Essentiality tests suggested that neither sig1 nor sig2 is essential under all conditions.
However, as some large molecules may not be broken down, we still kept the uptakes for these molecules in two cases: 1) if their uptakes was added during the correction of a false gene essentiality prediction (for example, fatty acids); and 2) if deletions of these uptakes caused a growth rate lower than the defined threshold or generated new false gene essentiality predictions.
So the epistemic essentiality claim seems right.
Figure 4: Validation of predicted gene essentiality in ccRCC.
There is a notion of museum essentiality that is by no means beyond debate".
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Justyna Jupowicz-Kozak
CEO of Professional Science Editing for Scientists @ prosciediting.com