​Variability in the molecules of life

How variable are gene transcripts and proteins, the molecules of life, across the tissues and organs of the human body? Furthermore, how variable are they within the same tissue type from different people? Understanding this variability will be key for the realisation of personalised medicine. These questions are the focus of a new study led by researchers from Uppsala University, which is published in NAR Genomics and Bioinformatics.

“We noticed that the variability in abundance in different tissue types was higher on the protein level than on the transcript level, which indicates that data from both the transcript and protein levels is necessary to understand a biological system,” says Christine Wegler, researcher in the Drug Delivery Group headed by Professor Per Artursson at the Department of Pharmacy, Uppsala University, and SciLifeLab, Sweden.

In the flow of biological information, the genes in our DNA are first read and replicated as transcripts, also known as messenger RNAs (mRNAs). These transcripts are then translated into proteins, which carry out the intended biological function. The abundances of these important molecules throughout the human body have been well characterised, but direct comparisons of variability patterns at the transcript and protein levels have been less comprehensive. Any discrepancies in variability between the transcript and protein levels could have implications for the regulation of information flow from gene to protein. In addition, a closer look at the variability within the same tissue type from multiple donors could provide essential information for personalised treatment in certain disease states.

Professor Per Artursson’s research group has combined publicly available transcriptomics and proteomics data with a new in-house dataset of protein concentrations in the liver and small intestine (jejunum) from 38 human donors. They found that transcript variability across tissue types was not well reflected at the protein level, and that protein abundances vary more across different tissues than transcript abundances.

An in-depth analysis of protein abundance variability in the liver and small intestine showed that some proteins were present at similar levels in the respective tissues across all donors, while other proteins varied widely also within the same tissue type.

“We found that proteins that are essential for cell survival had similar abundances across the different donors, showing that cells need to maintain consistent levels of these proteins. In contrast, many of the most variable proteins within tissues were related to disease, leading us to suggest that variability analysis could be a simple tool in the early stages of biomarker discovery. Our study thus not only provides insight on basic biology, but can also contribute to advancing the field of personalised medicine by highlighting protein abundance differences within the same tissue type from different people,” says Christine Wegler.

Wegler, C., Ölander, M., Wiśniewski, J.R., Lundquist, P., Zettl, K., Åsberg, A., Hjelmesæth, J., Andersson, T.B., Artursson, P. (2019) NAR Genomics and Bioinformatics, Volume 2, Issue 1, March 2020, lqz010, https://doi.org/10.1093/nargab/lqz01

For further information:

Christine Wegler, researcher at the Department of Pharmacy, Uppsala University, and SciLifeLab, Sweden. christine.wegler@farmaci.uu.se

Per Artursson, Professor at the Department of Pharmacy, Uppsala University, and SciLifeLab, per.artursson@farmaci.uu.se