Test the combination against the network
An individual-target ranking tells you which nodes look attractive. In the KRAS-related model, interventions and adaptation change a flow network; the remaining paths show why a proposed combination may still leave signaling capacity. The result is a specific bypass hypothesis to test.
The graph is an explicit hypothesis
Its capacities are hand-set ordinal values, not measured biological rates. The analysis cannot predict patient response from a network diagram. It is most useful when the encoded route can be checked against perturbation evidence in the relevant cell model.
Protein and transcript are different intervention points
Co-targeting may act on protein activity, transcript production or both. Isoform context can change which of those choices makes biological sense. A proposed combined workflow must preserve that context rather than treating every gene product as equivalent.
- Isoform-specific assessment · Check which transcript and protein product the intervention should affect. Isoform-specific assessment
- Antisense strategies · See the current support for transcript-directed interventions. Antisense strategies
Test the escape, then the pair
Use single and combined perturbations to ask whether the nominated bypass controls the response. That experiment can support the model, expose a missing route or remove the rationale for the combination.