Faculty of Computer and Information Science, University of Ljubljana, Ljubljana, Slovenia.
PLoS One. 2024 Jun 11;19(6):e0304102. doi: 10.1371/journal.pone.0304102. eCollection 2024.
Boolean networks provide an effective mechanism for describing interactions and dynamics of gene regulatory networks (GRNs). Deriving accurate Boolean descriptions of GRNs is a challenging task. The number of experiments is usually much smaller than the number of genes. In addition, binarization leads to a loss of information and inconsistencies arise in binarized time-series data. The inference of Boolean networks from binarized time-series data alone often leads to complex and overfitted models. To obtain relevant Boolean models of gene regulatory networks, inference methods could incorporate data from multiple sources and prior knowledge in terms of general network structure and/or exact interactions. We propose the Boolean network inference method SAILoR (Structure-Aware Inference of Logic Rules). SAILoR incorporates time-series gene expression data in combination with provided reference networks to infer accurate Boolean models. SAILoR automatically extracts topological properties from reference networks. These can describe a more general structure of the GRN or can be more precise and describe specific interactions. SAILoR infers a Boolean network by learning from both continuous and binarized time-series data. It navigates between two main objectives, topological similarity to reference networks and correspondence with gene expression data. By incorporating the NSGA-II multi-objective genetic algorithm, SAILoR relies on the wisdom of crowds. Our results indicate that SAILoR can infer accurate and biologically relevant Boolean descriptions of GRNs from both a static and a dynamic perspective. We show that SAILoR improves the static accuracy of the inferred network compared to the network inference method dynGENIE3. Furthermore, we compared the performance of SAILoR with other Boolean network inference approaches including Best-Fit, REVEAL, MIBNI, GABNI, ATEN, and LogBTF. We have shown that by incorporating prior knowledge about the overall network structure, SAILoR can improve the structural correctness of the inferred Boolean networks while maintaining dynamic accuracy. To demonstrate the applicability of SAILoR, we inferred context-specific Boolean subnetworks of female Drosophila melanogaster before and after mating.
布尔网络为描述基因调控网络(GRN)的相互作用和动态提供了有效的机制。推导出 GRN 的准确布尔描述是一项具有挑战性的任务。实验的数量通常远小于基因的数量。此外,二值化会导致信息丢失,并且在二值时间序列数据中会出现不一致。仅从二值时间序列数据推断布尔网络通常会导致复杂且过度拟合的模型。为了获得相关的基因调控网络布尔模型,可以根据一般网络结构和/或确切的相互作用,从多个来源和先验知识推断布尔网络。我们提出了布尔网络推理方法 SAILoR(基于结构的逻辑规则推理)。SAILoR 将时间序列基因表达数据与提供的参考网络结合起来,以推断准确的布尔模型。SAILoR 自动从参考网络中提取拓扑属性。这些属性可以描述 GRN 的更一般结构,也可以更精确并描述特定的相互作用。SAILoR 通过从连续和二值时间序列数据中学习来推断布尔网络。它在两个主要目标之间进行导航,即与参考网络的拓扑相似性和与基因表达数据的对应关系。通过合并 NSGA-II 多目标遗传算法,SAILoR 依赖于群体的智慧。我们的结果表明,SAILoR 可以从静态和动态两个角度推断出 GRN 的准确且具有生物学意义的布尔描述。我们表明,与 dynGENIE3 网络推断方法相比,SAILoR 提高了推断网络的静态准确性。此外,我们将 SAILoR 的性能与其他布尔网络推断方法(包括 Best-Fit、REVEAL、MIBNI、GABNI、ATEN 和 LogBTF)进行了比较。我们表明,通过合并关于整体网络结构的先验知识,SAILoR 可以提高推断的布尔网络的结构正确性,同时保持动态准确性。为了展示 SAILoR 的适用性,我们在雌性果蝇交配前后推断了特定于上下文的布尔子网。
PLoS One. 2024
BMC Bioinformatics. 2020-7-20
BMC Syst Biol. 2014-3-26
Bioinformatics. 2018-9-1
BMC Syst Biol. 2012-8-28
PLoS One. 2025-3-5
Bioinformatics. 2023-4-3
Proc Natl Acad Sci U S A. 2023-1-31
Nucleic Acids Res. 2022-7-5