@article {Cs{\'a}rdi009472, author = {G{\'a}bor Cs{\'a}rdi and Alexander Franks and David S. Choi and Edoardo M. Airoldi and D. Allan Drummond}, title = {Accounting for experimental noise reveals that transcription dominates control of steady-state protein levels in yeast}, elocation-id = {009472}, year = {2014}, doi = {10.1101/009472}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Cells respond to their environment by modulating protein levels through mRNA transcription and post-transcriptional control. Modest correlations between global steady-state mRNA and protein measurements have been interpreted as evidence that transcript levels determine roughly 40\% of the variation in protein levels, indicating dominant post-transcriptional effects. However, the techniques underlying these conclusions, such as correlation and regression, yield biased results when data are noisy, missing systematically, and collinear{\textemdash}properties of mRNA and protein measurements{\textemdash}which motivated us to revisit this subject. Noise-robust analyses of 25 studies of budding yeast reveal that mRNA levels explain roughly 80\% of the variation in steady-state protein levels. Post-transcriptional regulation amplifies rather than competes with the transcriptional signal. Measurements are highly reproducible within but not between studies, and are distorted in part by between-study differences in gene expression. These results substantially revise current models of protein-level regulation and introduce multiple noise-aware approaches essential for proper analysis of many biological phenomena.}, URL = {https://www.biorxiv.org/content/early/2014/09/21/009472}, eprint = {https://www.biorxiv.org/content/early/2014/09/21/009472.full.pdf}, journal = {bioRxiv} }