Figure 1.

Systems biology analysis workflow. (a) Multi-scale data collection (inputs). (b) Systems computational approaches for hypothesis testing. Enriched gene-sets gain overlap at the biological pathway level. Thus, we identified recurrently dysregulated pathways and pathway genes from multi-scale data. Subsequently, we identified critical topological features from the HR-NB-associated PPI subnetwork. Finally, we scanned pharmacological agents for the over-representation of their interacting targets among the gene signatures that were recurrent at the pathway and protein levels. Notably, this computational work links clinical relevance to an ESC-like signal. (c) Generation of new hypotheses based on the above computational analysis and literature review and the subsequent design of biological experiments. (d) Biological in vitro evaluation and clinical application validated for data from independent patients.