Researchers from the Swiss Federal Institute of Technology in Lausanne (EPFL) and the Swiss Federal Institute of Technology in Zurich (ETH; both Switzerland) have developed an analytical tool for determining the inherent biological differences between individuals. The SWATH-MS technique permits researchers to assess individual differences, for example in metabolism, and provides further tools in the move towards personalized medicine.
When treating conditions such as diabetes, obesity and fatty liver, there is variation in the way different patients respond to treatment. This variation is due to inherent differences between individuals, which mean it is difficult to create standard treatments that will work for all patients.
At present, it is mostly only genetic differences that are taken into account when personalizing treatments for patients, whereas a number of factors – including an individuals’ genome, proteome, fats etc. – contribute to variation in responses to treatment. In this new study on mice, APFL and ETH researchers developed a new method to compare the genome and proteome of an individual.
“It’s much more complex to measure the set of proteins than to sequence the entire genome,” commented Yibo Wu, co-lead author. To do this, they utilized a MS technique developed by Ruedi Aebersold’s (ETH) group: SWATH-MS. The technique combines the benefits of high-throughput MS with additional consistency and high reproducibility, allowing the identification of thousands of different proteins in a sample in a much quicker time than conventional techniques.
The team utilized SWATH-MS to measure concentrations of a broad spectrum of liver proteins in mice across 40 different mouse strains, all of which came from two common ancestors. This allowed the researchers to observe the effects of diet on the proteome and other factors without genetic interference.
By charting physiological data and combining it with the data on the mice’s genome and proteome, the team were able to understand the role that individual differences play in metabolism and energy production in mice. With the success of this study, the team hope that these techniques, including SWATH-MS, can be carried over to benefit patients in the clinical environment.
“Like the mouse strains in this study, each patient with a disease is genetically different”, explained Aebersold. “The approach we used in the mouse cohort can now be applied one-for-one in research on human diseases, and particularly for personalized medicine.” The authors highlight that the SWATH-MS approach is now ready for use in human cohort studies – the researchers have already created a human protein database.
“The aim here is to be able to customise medical intervention for each patient based on their individual biological makeup, the ‘black box’,” added Johan Auwerx (EPFL).
Sources: Williams EG, Wu Y, Jha P et al. Systems proteomics of liver mitochondria function. Science doi:10.1126/science.aad0189 (2016) (Epub ahead of print); https://actu.epfl.ch/news/a-new-tool-brings-personalized-medicine-closer/