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Predictive combustion models are useful tools towards the development of clean and efficient engines operating with alternative fuels. This work intends to validate two different combustion models on compression-ignition engines fueled with Dimethyl Ether. Both approaches give a detailed characterization of the combustion kinetics, but they substantially differ in how the interaction between fluid-dynamics and chemistry is treated. The first one is single-flamelet Representative Interactive Flamelet, which considers turbulence-kinetic interaction but cannot correctly describe the stabilization of the flame. The second, named Tabulated Well Mixed, correctly accounts for local flow and mixture conditions but does not consider interaction between turbulence and chemistry. An experimental campaign was carried out on a heavy-duty truck engine running on DME at a constant load considering trade-off of EGR and SOI.