In this paper, a novel methodology for highlevel modeling of bus communication in embedded systems is introduced. It allows the dynamic evaluation of their signal integrity (SI) characteristics at the virtual prototyping step (i.e., before physical realization). The method is based on the association of functional and nonfunctional modules. Functional modules represent the ideal behavior of the system, while nonfunctional modules use neural networks to model SI effects. This approach was implemented in SystemC-AMS, using the timed data flow model of computation. The method is illustrated by a Universal Serial Bus (USB) 3.0 application, where modular and parameterizable models are introduced. The method achieved good accuracy (<5%) while allowing significant simulation speedup (up to 2000 times), compared with SPICE-based reference models. This methodology can be used to perform an early SI analysis in the virtual prototyping of bus communication in the embedded systems.