Abstract Observing behaviors of protein pathways and genetic networks under various environments in living cells is essential for unraveling disease and developing drugs. For that purpose, the biological experimental technique using transfected cell microarrays (cell arrays) has been developed. In order to apply cell arrays to identification of the subnetworks that are significantly activated or inactivated by external signals or environmental changes, it is useful to allocate several or several tens of reporter genes. In this paper, we consider the problem of selecting the most effective set of reporter genes. We propose two graph theoretic formulations of the reporter gene allocation problem, and show that both problems are hard to approximate. We propose integer programming-based methods for solving practical instances of these problems optimally. We apply them to apoptosis pathway maps, and discuss biological significance of the result. We also apply them to artificial scale-free n...