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One important aspect of computational systems biology includes the identification and analysis of functional response networks within large biochemical networks. These functional response networks represent the response of a biological system under a particular experimental condition which can be used to pinpoint critical biological processes.For this purpose, we have developed a novel algorithm to calculate response networks as scored/weighted sub-graphs spanned by k-shortest simple (loop free) paths. The k-shortest simple path algorithm is based on a forward/backward chaining approach synchronized between pairs of processors. The algorithm scales linear with the number of processors used. The algorithm implementation is using a Linux cluster platform, MPI lam and mpiJava messaging as well as the Java language for the application.The algorithm is performed on a hybrid human network consisting of 45,041 nodes and 438,567 interactions together with gene expression information obtained from human cell-lines infected by influenza virus. Its response networks show the early innate immune response and virus triggered processes within human epithelial cells. Especially under the imminent threat of a pandemic caused by novel influenza strains, such as the current H1N1 strain, these analyses are crucial for a comprehensive understanding of molecular processes during early phases of infection. Such a systems level understanding may aid in the identification of therapeutic markers and in drug development for diagnosis and finally prevention of a potentially dangerous disease.