A general framework for interoperability with applications to healthcare

•Provide a formal method to define the interoperability of a system composed of modules that need to exchange data.•An Interoperability Matrix and its associated Interoperability Flow Graph represent different types of interoperability between related applications.•This formal representation is useful for flow graph algorithms that determine interoperability traits within a group of related applications.•The reduce cost of achieving interoperability is short-term and incurred in the design phase, while the benefit reaped is long-term.