School of Mathematical Sciences, Xiamen University, Zengcuo'an West Road, Siming District, Xiamen 361000, China.
Brief Bioinform. 2024 Jul 25;25(5). doi: 10.1093/bib/bbae396.
Constructing gene regulatory networks is a widely adopted approach for investigating gene regulation, offering diverse applications in biology and medicine. A great deal of research focuses on using time series data or single-cell RNA-sequencing data to infer gene regulatory networks. However, such gene expression data lack either cellular or temporal information. Fortunately, the advent of time-lapse confocal laser microscopy enables biologists to obtain tree-shaped gene expression data of Caenorhabditis elegans, achieving both cellular and temporal resolution. Although such tree-shaped data provide abundant knowledge, they pose challenges like non-pairwise time series, laying the inaccuracy of downstream analysis. To address this issue, a comprehensive framework for data integration and a novel Bayesian approach based on Boolean network with time delay are proposed. The pre-screening process and Markov Chain Monte Carlo algorithm are applied to obtain the parameter estimates. Simulation studies show that our method outperforms existing Boolean network inference algorithms. Leveraging the proposed approach, gene regulatory networks for five subtrees are reconstructed based on the real tree-shaped datatsets of Caenorhabditis elegans, where some gene regulatory relationships confirmed in previous genetic studies are recovered. Also, heterogeneity of regulatory relationships in different cell lineage subtrees is detected. Furthermore, the exploration of potential gene regulatory relationships that bear importance in human diseases is undertaken. All source code is available at the GitHub repository https://github.com/edawu11/BBTD.git.
构建基因调控网络是一种广泛应用于研究基因调控的方法,在生物学和医学中有多种应用。大量的研究集中在使用时间序列数据或单细胞 RNA 测序数据来推断基因调控网络。然而,这些基因表达数据要么缺乏细胞信息,要么缺乏时间信息。幸运的是,延时共聚焦激光显微镜的出现使生物学家能够获得秀丽隐杆线虫的树状基因表达数据,实现了细胞和时间分辨率。尽管这种树状数据提供了丰富的知识,但它们也带来了一些挑战,例如非成对时间序列,导致下游分析的不准确性。为了解决这个问题,提出了一种全面的数据集成框架和一种基于具有时滞的布尔网络的新贝叶斯方法。预筛选过程和马尔可夫链蒙特卡罗算法被应用于获取参数估计。模拟研究表明,我们的方法优于现有的布尔网络推断算法。利用提出的方法,基于秀丽隐杆线虫的真实树状数据集,重建了五个子树的基因调控网络,其中恢复了一些先前遗传研究中证实的基因调控关系。此外,还检测到不同细胞谱系子树中调控关系的异质性。此外,还探索了在人类疾病中具有重要意义的潜在基因调控关系。所有的源代码都可以在 GitHub 存储库 https://github.com/edawu11/BBTD.git 上获得。
PLoS One. 2014-12-31
Genes Genomics. 2019-2-11
BMC Bioinformatics. 2024-5-9
BMC Bioinformatics. 2016-9-6
Bioinformatics. 2020-12-30
Comput Biol Med. 2014-5
Genetics. 2024-5-7
Biomolecules. 2023-3-5
PLoS Comput Biol. 2023-3
Innovation (Camb). 2021-7-1
Bioinformatics. 2020-1-15
Methods Mol Biol. 2018
Biochim Biophys Acta Gene Regul Mech. 2016-9-16
BMC Bioinformatics. 2015