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Mechanistic ODE models encode pathway topology but are blind to anything outside the pathway. Representation learning compresses data into low-dimensional embeddings but says nothing about mechanism. Deep Mechanistic Models (DMMs) are our attempt at both in one model www.biorxiv.org/content/10.6...

DMMs couple semi-supervised representation learning to an ODE model of EGFR/MAPK signalling, end-to-end. The encoder proposes cell-line-specific parameters; the ODE model tests them against dynamic perturbation data. Representation and mechanism constrain each other rather than sitting side by side.

Per usual, mechanistic models stay informative where they fail: DMMs systematically underpredict phospho-ERK under MEK inhibition, which could reflect unmodelled crosstalk with AMPK signalling.

Data-driven integration calls breast cancer subtype important; supply EGFR levels to the ODE instead and the subtype signal vanishes. Two explanations with same predictive power so the data cannot arbitrate between a molecular and a systems lens. DMMs surface the ambiguity and let us be the judge.