Faculty of Natural Sciences and Mathematics, University of Maribor, Maribor, Slovenia.
Faculty of Medicine, University of Maribor, Maribor, Slovenia.
PLoS Comput Biol. 2024 May 13;20(5):e1012130. doi: 10.1371/journal.pcbi.1012130. eCollection 2024 May.
Within the islets of Langerhans, beta cells orchestrate synchronized insulin secretion, a pivotal aspect of metabolic homeostasis. Despite the inherent heterogeneity and multimodal activity of individual cells, intercellular coupling acts as a homogenizing force, enabling coordinated responses through the propagation of intercellular waves. Disruptions in this coordination are implicated in irregular insulin secretion, a hallmark of diabetes. Recently, innovative approaches, such as integrating multicellular calcium imaging with network analysis, have emerged for a quantitative assessment of the cellular activity in islets. However, different groups use distinct experimental preparations, microscopic techniques, apply different methods to process the measured signals and use various methods to derive functional connectivity patterns. This makes comparisons between findings and their integration into a bigger picture difficult and has led to disputes in functional connectivity interpretations. To address these issues, we present here a systematic analysis of how different approaches influence the network representation of islet activity. Our findings show that the choice of methods used to construct networks is not crucial, although care is needed when combining data from different islets. Conversely, the conclusions drawn from network analysis can be heavily affected by the pre-processing of the time series, the type of the oscillatory component in the signals, and by the experimental preparation. Our tutorial-like investigation aims to resolve interpretational issues, reconcile conflicting views, advance functional implications, and encourage researchers to adopt connectivity analysis. As we conclude, we outline challenges for future research, emphasizing the broader applicability of our conclusions to other tissues exhibiting complex multicellular dynamics.
在胰岛中，β 细胞协调胰岛素的同步分泌，这是代谢稳态的关键方面。尽管单个细胞具有固有异质性和多模态活性，但细胞间耦合起着均匀化的作用，通过细胞间波的传播实现协调反应。这种协调的破坏与不规则的胰岛素分泌有关，这是糖尿病的一个标志。最近，出现了一些创新方法，如将多细胞钙成像与网络分析相结合，用于定量评估胰岛中的细胞活性。然而，不同的研究组使用不同的实验方案、显微镜技术，应用不同的方法来处理测量信号，并使用各种方法来推导出功能连接模式。这使得在发现之间进行比较和将其纳入更广泛的图景变得困难，并导致了对功能连接解释的争议。为了解决这些问题，我们在这里系统地分析了不同方法如何影响胰岛活性的网络表示。我们的研究结果表明，构建网络所使用的方法的选择并不关键，尽管需要注意从不同胰岛中组合数据。相反，网络分析得出的结论可能会受到时间序列预处理、信号中振荡分量的类型以及实验方案的严重影响。我们的教程式研究旨在解决解释问题、调和冲突观点、推进功能意义，并鼓励研究人员采用连接分析。在结论中，我们概述了未来研究的挑战，强调了我们的结论对其他表现出复杂多细胞动力学的组织的更广泛适用性。
