Department of Bioinformatics-BiGCaT, School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands.
RECETOX, Faculty of Science, Masaryk University, Kotlarska 2, 611 37, Brno, Czech Republic.
Brief Bioinform. 2024 Sep 23;25(6). doi: 10.1093/bib/bbae569.
Systems biology aims to understand living organisms through mathematically modeling their behaviors at different organizational levels, ranging from molecules to populations. Modeling involves several steps, from determining the model purpose to developing the mathematical model, implementing it computationally, simulating the model's behavior, evaluating, and refining the model. Importantly, model simulation results must be reproducible, ensuring that other researchers can obtain the same results after writing the code de novo and/or using different software tools. Guidelines to increase model reproducibility have been published. However, reproducibility remains a major challenge in this field. In this paper, we tackle this challenge for physiologically-based pharmacokinetic (PBPK) models, which represent the pharmacokinetics of chemicals following exposure in humans or animals. We summarize recommendations for PBPK model reporting that should apply during model development and implementation, in order to ensure model reproducibility and comprehensibility. We make a proposal aiming to harmonize abbreviations used in PBPK models. To illustrate these recommendations, we present an original and reproducible PBPK model code in MATLAB, alongside an example of MATLAB code converted to Systems Biology Markup Language format using MOCCASIN. As directions for future improvement, more tools to convert computational PBPK models from different software platforms into standard formats would increase the interoperability of these models. The application of other systems biology standards to PBPK models is encouraged. This work is the result of an interdisciplinary collaboration involving the ELIXIR systems biology community. More interdisciplinary collaborations like this would facilitate further harmonization and application of good modeling practices in different systems biology fields.
系统生物学旨在通过在不同的组织层次上对生物体的行为进行数学建模来理解生物体，这些层次从分子到群体不等。建模涉及多个步骤，从确定模型目的到开发数学模型，再到通过计算实现、模拟模型行为、评估和完善模型。重要的是，模型模拟结果必须是可重现的，以确保其他研究人员在重新编写代码和/或使用不同的软件工具后可以获得相同的结果。已经发布了提高模型可重现性的指南。然而，在这个领域，可重现性仍然是一个主要挑战。在本文中，我们针对基于生理学的药代动力学（PBPK）模型解决了这一挑战，这些模型代表了化学物质在人类或动物暴露后的药代动力学。我们总结了 PBPK 模型报告的建议，这些建议应在模型开发和实施过程中适用，以确保模型的可重现性和可理解性。我们提出了一个旨在协调 PBPK 模型中使用的缩写的建议。为了说明这些建议，我们在 MATLAB 中展示了一个原始且可重现的 PBPK 模型代码，并提供了一个使用 MOCCASIN 将 MATLAB 代码转换为系统生物学标记语言格式的示例。作为未来改进的方向，更多将不同软件平台的计算性 PBPK 模型转换为标准格式的工具将提高这些模型的互操作性。鼓励将其他系统生物学标准应用于 PBPK 模型。这项工作是涉及 ELIXIR 系统生物学社区的跨学科合作的结果。更多像这样的跨学科合作将促进不同系统生物学领域的良好建模实践的进一步协调和应用。
