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International audienceThis book constitutes the refereed proceedings of the 15th International Conference on Computational Methods in Systems Biology, CMSB 2017, held in Darmstadt, Germany, in September 2017. The 15 full papers, 4 tool papers and 4 posters presented together with 1 invited talk were carefully reviewed and selected from 41  regular paper submissions. Topics of interest include formalisms for modeling  biological processes; models and their biological applications; frameworks for model verication, validation, analysis, and simulation of biological systems; high-performance computational systems biology and parallel implementations; model inference from experimental data; model integration from biological databases; multi-scale modeling and analysis methods; and computational approaches for synthetic biology