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Upadhya, S. R.

Publications and source records attributed to Upadhya, S. R..

2 recordsLinked to original sources

Antibody reliability influences observed mRNA-protein correlations in tumour samples

Reverse phase protein arrays (RPPA) have been used to quantify the abundances of hundreds of proteins across thousands of tumour samples in the Cancer Genome Atlas (TCGA). By number of samples, this is the largest tumour proteomic dataset available and it provides an opportunity to systematically assess the correlation between mRNA and protein abundances. However, the RPPA approach is highly dependent on antibody reliability and approximately one third of the antibodies used in the TCGA are deemed to be somewhat less reliable. Here, we assess the impact of antibody reliability on observed mRNA-protein correlations. We find that, in general, proteins measured with less reliable antibodies have lower observed mRNA-protein correlations. This is not true of the same proteins when measured using mass spectrometry. Furthermore, in cell lines, we find that when the same protein is quantified by both mass spectrometry and RPPA, the overall correlation between the two measurements is lower for proteins measured with less reliable antibodies. Overall our results reinforce the need for caution in using RPPA measurements from less reliable antibodies.

systems biology↗

Experimental reproducibility limits the correlation between mRNA and protein abundances in tumour proteomic profiles

Large-scale studies of human proteomes have revealed only a moderate correlation between mRNA and protein abundances. It is unclear to what extent this moderate correlation reflects post-transcriptional regulation and to what extent it reflects measurement error. Here, by analysing replicate profiles of tumours and cell lines, we show that there is considerable variation in the reproducibility of measurements of transcripts and proteins from individual genes. Proteins with more reproducible measurements tend to have higher mRNA-protein correlation, suggesting that measurement reproducibility accounts for a substantial fraction of the unexplained variation between mRNA and protein abundances. The reproducibility of individual proteins is somewhat consistent across studies and we exploit this to develop an aggregate reproducibility score that explains a substantial amount of the variation in mRNA-protein correlation across multiple studies. Finally, we show that pathways previously reported to have higher-than-average mRNA-protein correlation may simply contain members that can be more reproducibly quantified.

systems biology↗