EDUCATION :: MASS SPECTROMETRY
leading the way when it comes to overcoming them using the most advanced MS methods. An international multi-site study, conducted as part of the Cancer Moonshot initiative, recently applied many of the next-generation MS proteomics workflows high- lighted earlier to determine whether they could acceler- ate biomarker development. Using TMT multiplexing in discovery workflows for the large-scale analysis of human, yeast, and E. coli proteomes, each research group involved in the study analyzed a set of known proteins and com- pared their results to determine inter-lab and day-to-day measurement reproducibility. Label-free DDA-plus and HR-DIA workflows with precursor-level quantitation were subsequently used for verification and validation stud- ies, delivering comprehensive and accurate analysis that ensured remarkable reproducibility over large patient cohorts.
These MS-based workflows were used to enhance mea- surement reproducibility across sites, ultimately provid- ing greater confidence in the experimental data generated and accelerating the translation of biomarkers for detect- ing, monitoring, and treating cancer. Eleven international labs, including six Cancer Moonshot initiative labs, tested the protocols across biomarker identification, verification, and validation stages. In total, over 80 percent of the indi- vidual proteins analyzed were identified and quantified in common across different days at the same site, while 80 percent of protein groups were quantified in common across different days and across different labs.
The study confirmed the new MS methods could be incorporated into standardized and high-throughput proteomics workflows to offer exceptional measurement robustness and enhanced scalability from discovery to val- idation. By implementing the latest MS-based approaches across the biomarker pipeline, the study demonstrated how these robust methods could help to accelerate the development of potential biomarkers into the clinic.
Conclusion To realize the full potential of protein biomarkers, the existing challenges around reproducibility and scalability encountered with traditional proteomics workflows must be overcome. The latest MS-based proteomics workflows are addressing these bottlenecks in the translational pipeline, helping to drive the development of protein biomarkers for cancer diagnosis, monitoring, and precision treatment.
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Yue Xuan, PhD, serves as a Senior Product Marketing Manager, Precision Medicine at Thermo Fisher Scientific. She is specialized in multi-omics research including proteome profiling workflow development and is the project lead for the international Cancer Moonshot multi-site study. She has a MSc in chemistry from Free University Berlin and a PhD in chemistry from Technical University of Dortmund, Germany.
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