Synthesis of Ovarian Cancer Multi-Omics Datasets: A Biology-Informed Evaluation Framework

Paired multi-omic cancer cohorts are costly to assemble and difficult to share, motivating synthetic cohorts as a complementary resource. As generative model development accelerates, we shift the focus from proposing yet another architecture to defining evaluation criteria that determine whether synthetic data preserve biologically relevant structure. We introduce a biology-informed and patient-disjoint framework for evaluating the generation of paired RNA expression and copy-number variation (CNV) profiles, and apply it to the longitudinal DECIDER high-grade serous ovarian cancer cohort. The framework assesses modality-specific fidelity and coherence between RNA and CNV pairs using agreement between real training and held-out data as a reference, alongside complementary training-data proximity diagnostics. We adapt three multi-omic integration architectures based on variational autoencoders to generate paired profiles. The model leading several fidelity and coherence measures also shows the strongest training-data proximity. The protocol and case study offer the community a reference for comparing future multi-omic generators and extending their evaluation to clinical prediction.