布尔网络建模及其与实验读数的整合:使用白血病模型的跨学科演示。

Julia Maier, Julian D Schwab, Silke D Werle, Ralf Marienfeld, Peter Möller, Nadine T Gaisa, Nensi Ikonomi, Hans A Kestler
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引用次数: 0

摘要

合适的动物模型和细胞系有限,往往会阻碍癌症实验研究。湿法实验室实验也耗时费钱。在这篇综述中,我们介绍了一种硅学建模策略,即布尔网络(BN)模型,并展示了如何将其应用于简化实验设计和集中实验读数的工作。布尔网络模型可对大型分子信号通路及其交叉关系进行动态分析。在建立和验证特定肿瘤模型后,通过研究不同肿瘤表型的轨迹,可以获得对肿瘤细胞行为的机理认识。此外,还可以进行肿瘤驱动因素和药物靶点筛选。这些自动筛选有助于确定新的干预靶点和肿瘤演变的潜在生物标志物,从而指导新的湿实验室实验。本综述的目的是利用慢性淋巴细胞白血病(CLL)BN 模型,展示如何在经典湿实验室研究中建立、验证和使用 BN 建模及其相关技术。
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Boolean network modeling and its integration with experimental read-outs : An interdisciplinary presentation using a leukemia model.

The limited availability of suitable animal models and cell lines often impedes experimental cancer research. Wet-laboratory experiments are also time-consuming and cost-intensive. In this review, we present an in silico modeling strategy, namely, Boolean network (BN) models, and demonstrate how it could be applied to streamline experimental design and to focus the effort of experimental read-outs. Boolean network models allow for the dynamic analysis of large molecular signaling pathways and their crosstalks. After establishing and validating a specific tumor model, mechanistic insights into the tumor cell behavior can be gained by studying the trajectories of different tumor phenotypes. Also, tumor driver and drug target screenings can be performed. These automatic screenings can help to identify new intervention targets and putative biomarkers for tumor evolution, hence guiding new wet-laboratory experiments. The goal of this round-up is to demonstrate how to establish, validate, and use BN modeling and its crosstalks in classic wet-laboratory research using a chronic lymphocytic leukemia (CLL) BN model.

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