Proteomics is a state-of-the-art method for biomarker discovery, yet its application as an analytical diagnostic tool is currently limited due to technical challenges. Characterizing and diagnosing rare diseases in the pediatric field with traditional single-readout methods is challenging and could benefit significantly from the routine acquisition of proteomics data. Our aim is to unlock insights into pediatric disease mechanisms by characterizing proteomic profiles in the pediatric population, thereby enhancing early diagnosis and intervention strategies through advanced mass spectrometry (MS)-based proteomics.

To enable the diagnostic application of proteomics for individual patients, a thorough understanding of the population proteome is required. By mapping covariate-dependent variances, we can define and differentiate proteome signatures of disease from physiological and developmental processes. Among other large cohorts, we are systematically profiling the blood plasma and urinary proteomes of over 5,000 pediatric subjects using MS-based proteomics to establish a comprehensive proteome profile database. This involves a detailed analysis of population variance, disease-related proteomic changes, and the impact of monogenetic diseases. The resulting data will serve as a reference for future proteome analyses, aiming to integrate proteomic information into routine diagnostic practices. For specific disease phenotypes, additional specimens are analyzed to link patterns across different matrices. For example, co-analysis of plasma and intestinal biopsies in conditions such as very early onset intestinal bowel disease provides deeper insights into the disease mechanisms. Parallel in-vitro investigations using induced pluripotent stem (iPS) cells and organoids help to characterize monogenetic drivers and delineate molecular disease etiologies at the proteome level. These studies complement our profiling efforts, allowing us to explore the functional implications of identified proteomic changes.

Preliminary data from plasma and urine proteomes reveal distinct proteomic signatures within the pediatric population, defining both normal and aberrant proteomic landscapes. Initial findings suggest novel covariate-dependent protein biomarkers and adverse proteomic trajectories associated with specific pediatric diseases. The integration of comprehensive proteomic profiling with in-vitro studies advances our understanding of pediatric disease biology. Our research has the potential to refine the precision of early diagnosis and pave the way for innovative developments in systemic and disease-overarching pediatric research. We believe our findings will support the development of tailored diagnostic and therapeutic strategies in precision medicine, benefiting both pediatric and adult populations. Pediatric patients with rare disease conditions can act as key drivers of novel findings, with broad relevance for physiology and disease biology.