Fig. 8: Functional interaction network of AML-associated genes revealing key proteins and pathways targeted by LS and RU combinatorial therapies.
From: Solubility based mechanistic profiling of combinatorial drug therapy
A The network was constructed by integrating Reactome signaling interactions with high-confidence AML-associated genes derived from DepMap and the mutation data of the FIMM-AML cohort study (p < 0.001, high-impact variants). Directed shortest paths between all AML-associated protein pairs were used to define an induced subnetwork. Community detection using the Infomap algorithm identified 44 discrete clusters. Clusters with ≥ 15 genes overlapping CoPISA solubility shifts are highlighted in color. B Key AML-related proteins significantly altered by LS or RU, as detected by CoPISA solubility shifts, are highlighted, illustrating treatment-specific perturbations across the network. Created in BioRender. Gholizadeh, E. (2026) BioRender.com/mxrji5o (C) Each cluster is annotated via Reactome pathway enrichment (p.adj < 0.05), highlighting distinct functional modules. For clarity, two representative umbrella pathways per cluster are shown, capturing the dominant biological themes. P-values were adjusted for multiple testing using the Benjamini–Hochberg method. Pathways with adjusted P < 0.05 were considered significant. Source data are provided as a Source Data File.
