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In these analyses, we used counts per million (CPM) values normalized with the upper quartile normalization method, excluding genes with low read abundance due to the pronounced differences in library sizes between TCGA and GTEx (Supplementary Fig. 2).
To reduce variation between microarrays, the intensity values for samples in each microarray were rescaled using a quartile normalization method in the BeadStudio module.
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Read counts of the libraries were normalized using the Upper-Quartile Normalization method [ 19], and were then loge (ln) transformed, yielding transformed normalized counts.
For genes that had CPM less than 10, we considered the aligned reads as noise and set their expression level to 0. For expressed genes, we normalized the raw read counts using the upper-quartile normalization method [ 62].
We then normalized the raw read counts of expressed genes using the upper-quartile normalization method.
Enzyme activity and gene expression data are corrected with age and gender and then are normalized with normal quartile normalization.
The PLIER method uses quartile normalization and runs an optimization procedure which determines the best set of weights on the perfect match (PM) and mismatch (MM) for each probe pair.
Microarray data were normalized using median normalization method.
While in the UpQu normalization method, counts are normalized by division (in a given replicate) by the upper quartile of these counts, the Medi simply computes the median, and the ToCo uses the sum of all counts.
The selected normalization method (tested mean and quartile normalization) and bgThreshold (tested 50, 100, and 150) is the combination that resulted in the most significant enrichment of slow growing strains identified in the heterozygous deletion pool, sampled every two generations for 20 generations (data not shown), with slow growers identified in a previous study [ 22].
Data were log2 transformed and quartile normalization was used to normalize data across samples.
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