Stock Marco, Losert Corinna, Zambon Matteo, Popp Niclas, Lubatti Gabriele, Hörmanseder Eva, Heinig Matthias, Scialdone Antonio
Helmholtz Center Munich Institute of Epigenetics und Stem Cells, Munich, Germany.
Helmholtz Center Munich Institute of Computational Biology, Munich, Germany.
Mol Syst Biol. 2025 Mar;21(3):214-230. doi: 10.1038/s44320-025-00088-3. Epub 2025 Feb 12.
Many studies have used single-cell RNA sequencing (scRNA-seq) to infer gene regulatory networks (GRNs), which are crucial for understanding complex cellular regulation. However, the inherent noise and sparsity of scRNA-seq data present significant challenges to accurate GRN inference. This review explores one promising approach that has been proposed to address these challenges: integrating prior knowledge into the inference process to enhance the reliability of the inferred networks. We categorize common types of prior knowledge, such as experimental data and curated databases, and discuss methods for representing priors, particularly through graph structures. In addition, we classify recent GRN inference algorithms based on their ability to incorporate these priors and assess their performance in different contexts. Finally, we propose a standardized benchmarking framework to evaluate algorithms more fairly, ensuring biologically meaningful comparisons. This review provides guidance for researchers selecting GRN inference methods and offers insights for developers looking to improve current approaches and foster innovation in the field.
许多研究使用单细胞RNA测序(scRNA-seq)来推断基因调控网络(GRN),这对于理解复杂的细胞调控至关重要。然而,scRNA-seq数据固有的噪声和稀疏性给准确的GRN推断带来了重大挑战。本综述探讨了一种为应对这些挑战而提出的有前景的方法:将先验知识整合到推断过程中,以提高推断网络的可靠性。我们对常见类型的先验知识进行了分类,如实验数据和精心策划的数据库,并讨论了表示先验知识的方法,特别是通过图结构。此外,我们根据最近的GRN推断算法纳入这些先验知识的能力对其进行分类,并评估它们在不同背景下的性能。最后,我们提出了一个标准化的基准测试框架,以更公平地评估算法,确保进行具有生物学意义的比较。本综述为研究人员选择GRN推断方法提供了指导,并为希望改进当前方法并推动该领域创新的开发者提供了见解。