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Batch normalization was performed using the median ratio for each metabolite in duplicate "anchor" samples across runs.
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Between-batch normalization was performed using Distance Weighted Discrimination (DWD) approach [ 19] using 4 samples replicated in the 2 microarray batches.
When the two data sets were combined for the integrative genomic analysis component, an additional quantile normalization was performed to adjust for batch effects between cohorts.
Normalization was performed within each dataset, and normalized expression values (log2 signal intensities) were corrected for batch effects across datasets using the COMBAT empirical Bayes method [ 54].
Quantile normalization was performed across the 3 microarray batches, all values <5 were replaced with the median of such values, and the value for each control cell line was set to the mean of its five replicates.
For the validation dataset [ 23], quantile normalization was performed and ANOVA was used to eliminate batch effects from different sample preparation methods, RNA extraction methods, different hybridization protocols and scanners.
The second normalization was performed in order to re-scale the intensity and also remove cross-platform batch effects using Combat function in SVA package [ 26].
Then, a second scaling normalization was performed to set the average expression on each chip to 1000 to reduce batch effects [ 15].
Quantile normalization was performed as implemented in the limma package.
Normalization was performed on the basal condition (no exogenous oxidant).
Normalization was performed with respect to the yield at negative time delays.
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