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Fig. 1 | Genome Biology

Fig. 1

From: Malignancy and NF-κB signalling strengthen coordination between expression of mitochondrial and nuclear-encoded oxidative phosphorylation genes

Fig. 1

High mitochondrial reads in GTEx libraries lead to artefactual correlations between genes using TPM normalisation, obscuring biological relationships. A Heatmap showing median Spearman’s correlation for mtOXPHOS and nuOXPHOS gene expression using TPM normalisation in 48 GTEx tissues combined (100 samples from each tissue, sampled 100 times). The order of genes for this and all mtOXPHOS-nuOXPHOS heatmaps throughout the paper is determined by the hierarchical clustering of correlations from Fig. 2A. B Violin plot showing total expression from mtDNA-encoded genes in samples from a selection of 15 healthy human tissues from the GTEx database. C Scatterplot shows median Spearman’s correlation (ρ) of mtOXPHOS-nuOXPHOS gene pairs within 48 GTEx tissues vs tissue mean of mtRNA levels as a percentage of total transcripts. Shown for data normalized by TPM, TPM excluding mitochondrial reads for normalizing nuclear genes, UQ, MRN and TMM methods. Error bars indicate IQR. Blue line shows linear regression with R2 and ρ noted within panel. D Scatterplot shows mean over 100 iterations of the tissue median ρ of mtOXPHOS with 126 random expressed nuclear genes vs tissue mean of mtRNA levels as a percentage of total transcripts. Shown for data normalized by TPM, TPM excluding mitochondrial reads for normalising nuclear genes, UQ, MRN and TMM methods. 95% confidence interval error bars are smaller than the plotted symbols. The blue line shows linear regression with R2 and ρ noted within panel. Green circles for MRN and TMM highlight unusually high correlations in the testis. E Scatterplot shows mean over 100 iterations of the tissue median ρ within 100 random expressed nuclear genes vs tissue mean of mtRNA levels as a percentage of total transcripts. Shown for data normalized by TPM, TPM excluding mitochondrial reads for normalising nuclear genes, UQ, MRN and TMM methods. 95% confidence interval error bars are smaller than the plotted symbols. The blue line shows linear regression with R2 and ρ noted within panel. Red circles for TPM highlight the whole blood and pancreas; green circles for MRN and TMM highlight unusually high correlations in the testis. F Boxplot shows mean values for 10 samples of the median ρ of 100 random expressed nuclear genes with TPM normalisation or TPM excluding the read counts for PRSS1 & PRSS2 (pancreas) or HBA1, HBA2, HBB and HBD (whole blood). G Scatterplot shows Spearman’s ρ within tissues for two genes, INSR and TSPAN5, for TPM normalized data and MRN normalized data. Colour indicates the tissue mean mtRNA level (% total transcripts). Tissues that fall in the top left quadrant are those in which the negative correlation observed using MRN normalisation has switched sign and appears to be positive using TPM normalisation

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