Cutting-edge genomic tools are redefining disease understanding and therapeutic strategies. Comprehensive tumor whole-genome sequencing at the Princess Máxima Center now guides pediatric oncology care by enabling precise classification and monitoring of cancer evolution. New Bayesian methods improve identification of transcriptional regulators in complex biological contexts, enhancing cancer biomarker discovery. Single-cell transcriptomics elucidate immune heterogeneity in systemic sclerosis, informing personalized treatments. Furthermore, cfDNA methylation profiling advances noninvasive liver transplant injury diagnostics by pinpointing cell-specific damage drivers, offering improved post-transplant care.