Central to the successful establishment of mass spectrometry for systems medicine in the neurosciences is the development of start-to-finish and fit-for-purpose workflows that address the many challenges inherent to analyzing clinical specimen from a complex disease background. Standardization is essential throughout starting with sample collection, to the bioinformatic methods taken for discovering and validating protein biomarkers. CLINSPECT-M is taking a systematic and graded approach to meeting the above requirements. We collaborate with the Joint Biobank Munich (JBM) which is part of the BMBF-funded German Biobank Alliance (GBA) and assess sample collection and storage protocols from the Munich biobanks and the external partners to identify potential confounding factors that negatively impact on proteomic measurements and discuss how these may be overcome and how potential changes can be implemented in sample collection or biobank standard operating procedures (SOPs).
The consortium partners deploy their respective current methods including LC-MS/MS hardware configurations and data processing approaches to the multi-replicate analysis of a standardized set of CSF, blood plasma, serum and tissue samples spiked with retention time standards in order to identify the current best practices in Munich. We pay particular attention to the future clinical applicability of the workflows including sensitivity, reproducibility, robustness and potential for automation. To make best practice methods available throughout the consortium, we will exchange personnel between partner sites for training purposes track changes in protocols over time. A second Munich-wide benchmarking study will be performed on the same samples to evaluate to which extent best practices can be transferred between laboratories, to identify areas where adjustments are required and to form the basis for defining analytical SOPs for these types of analytes. In addition, to foster exchange of experience beyond the Munich consortium and to further improve methodology, we will initiate a Germany-wide inter-laboratory comparison including other MScoreSys sites. This should eventually lead to national standards, transferable SOPs and high-quality training of analytical clinical personnel.
In this pursuit workpackage 5 brings together clinical experts around Prof. Daniel Teupser (Institute for Laboratory Medicine, Ludwigs Maximilians University of munich) and Prof. Wilko Weichert (Institute of General and Surgical Pathology, Technical University of Munich), proteomic know-how in the Munich area including the groups of Dr. Stefanie Hauck (Metabolomics and Proteomics Core, HMGU), Prof. Axel Imhof (Protein Analysis Unit, Ludwigs Maximilians University of Munich), Prof. Stefan Lichtenthaler (Chair for Neuroproteomics, Technical University of Munich), Prof. Bernhard Küster (Chair of Proteomics and Bioanalytics, Technical University of Munich), Prof. Matthias Mann (MPI for Biochemistry), Dr. Julia Mergner and Dr. Christina Ludwig (both BayBioMS), as well as bioinformatic expertise with Prof. Jürgen Cox (MPI for Biochemistry). This extraordinary team of experts from multiple disciplines puts a great effort into the successful establishment of mass spectrometry for systems medicine in the neurosciences.