Deliverable D2.3 V3 - Report Describing the Cross-Omics Demonstrators

We investigated to what extent metabolomic analysis would add to a genetic analysis of a complex rare genetic-metabolic disease. We analysed a cohort of 150 pediatric patients suffering from neurodevelopmental disorders, together with their parents, for genetic variants using whole genome and exome sequencing. Part of this cohort (40 patients) was suitable and was investigated for metabolic changes of a comprehensive targeted metabolite biomarker panel using mass spectrometry. We applied tools of the Multi-Omics Toolbox for data quality control and statistical analyses, to assess the utility and applicability of these tools in an independent cross-omics study.The study yielded a positive diagnosis of 30% of the 150 patients based on genetic analyses. The untargeted metabolomics data showed batch effects among the different runs which could successfully be corrected using the batch correction approaches from the EATRIS-Plus Multi-Omics Toolbox. Subsequent targeted metabolomic data analysis did not add functional diagnosis using the panel of 350 preselected and annotated metabolic biomarkers. We did observe differential metabolites which were seen in our diagnostic screening before but which are annotated as food-related and not relevant for diagnosis. The untargeted metabolomic data was made ready for extensive data analysis, which was beyond the scope of the current study.