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Mass spectrometric technology for next generation proteomics in systems medicine

Periodic Reporting for period 2 - MSmed (Mass spectrometric technology for next generation proteomics in systems medicine)

Reporting period: 2016-12-01 to 2018-05-31

The MSmed team’s vision is to make the large scale analysis of proteins - proteomics - a routine method for every biological laboratory and every clinic. In recent years, medicine has started to replace classical “one therapy for each disease” approaches with individual therapy regimens in the so-called “personalized medicine”. So far, such individualized therapies are based on the genetic profile of the patients, since these can be readily analyzed by state of the art technology.
Even more specific regimens might be possible if therapy decisions could be based on a patient’s actual profile of expressed genes, the proteins rather than his or her genetic disposition. Therefore, there is an urgent need to advance proteomics technologies from a specialist technology to a robust and powerful lab routine. This will help revolutionize diagnosis and prognosis based on the expression levels and modifications of proteins in cells, tissues, organoids or body fluids.
The applicants are leaders in proteomics technologies from academia and industry and have an out-standing track-record in advancing both instrumentation as well as its application in biological and disease contexts. Here we come together to develop breakthrough technology capable of more than a factor ten improvement in parameters of performance of the mass spectrometric workflow, enabling patient-oriented proteome profiling.
The proteomics workflow will be automated, multiplexed and made ‘industrial strength’-ready for high-throughput and in-depth clinical applications. Importantly, in addition to the identification of the main protein representative of a gene, we aim to routinely identify and quantify protein modifications and isoforms by using multidimensional approaches, including new separation, enrichment and fragmentation technologies. The breakthroughs aimed for will generate larger more biologically relevant data. This data will be merged with other ‘omic’ data and mined using machine learning technologies.
Our results will establish the role of mass spectrometry in systems medicine, making all workflows and mass spectrometry platforms available to the community. They will be used as the basis of myriad applications in biomedicine, even in the clinic. This in turn will lead to a new eco-system around improved diagnosis, elucidations of disease mechanisms and drug action.
Work in the first 30 months has already contributed to an improved mass spectrometry instrument, which was extensively tested in the partner labs and then commercially launched by partner Thermo Fisher Scientific in June 2017. Novel sample preparation techniques and analysis methods are reducing processing times. Along with this, novel software was developed to allow the quantitation of multiplexed samples and to detect post translational modifications, both indispensable features for the work with clinical samples. The partners are now bringing together these improvements in the development and validation of a highly streamlined workflow that will enable robust proteomics analysis of hundreds of patient samples.
MSmed is first and foremost a technological quantum jump and as such, its main impact will be in enabling an entire ecosystem of new applications of mass spectrometry. The new instrument will be commercially available and the protocols and software (MaxQuant) will be open access. Therefore, we expect very high uptake of the innovations produced in this EU grant.
Researchers and others using the technological platform will in turn be empowered to do things they could not have contemplated before. The genomics revolution is an example of what can be expected as a result. In that case, the introduction of NGS technology likewise made the technology a factor ten more powerful, which resulted in a tremendous boost for the application of genomics technology. Similarly, MSmed will break new ground. Simply put, mass spectrometry can be used in any area connected to the life science and by making this technology a factor ten more capable, we will create enormous multiplier effects.
In particular, we foresee a host of opportunities in health care. The transformation of proteome analysis into an automated routine tool will pave its way into the clinic. Proteome technology will be a game changer in personalized medicine. The actual medical parameters as reflected in the patient’s proteome, rather than solely genetic disposition, could then be applied in stratification of patient cohorts, individual treatment planning, and monitoring of response to therapy. Such improvements in personalized disease management would have a tremendous societal impact.
Furthermore, a huge economic impact can be expected since the new applications will offer a wide range of opportunities for established industries and start-ups in the development of innovative devices, targeted diagnostics and therapeutics. As a measure of scale, PricewaterhouseCoopers LLP in a 2009 report determined a market size for personalized medicine of $232 billion, with a growth potential of 10% annually, and estimated a market size of $42 billion by 2015 for the core medical device and diagnostics sector.