Insufficient performance of optimization approaches for fitting of mathematical models is still a major bottleneck in systems biology. In this manuscript, the reasons and methodological challenges are summarized as well as their impact in benchmark studies. Important aspects for increasing evidence of outcomes of benchmark analyses are discussed. Based on general guidelines for benchmarking in computational biology, a collection of tailored guidelines is presented for performing informative and unbiased benchmarking of optimization-based fitting approaches. Comprehensive benchmark studies based on these recommendations are urgently required for establishing of a robust and reliable methodology for the systems biology community.
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