Nantes Université, École Centrale Nantes, CNRS, LS2N, UMR 6004, F-44000, Nantes, France.
Department of Electronics, University of Frères Mentouri Constantine 1, Constantine, Algeria.
J Comput Biol. 2024 Jun;31(6):513-523. doi: 10.1089/cmb.2024.0517. Epub 2024 May 29.
Single-cell transcriptomic studies of differentiating systems allow meaningful understanding, especially in human embryonic development and cell fate determination. We present an innovative method aimed at modeling these intricate processes by leveraging scRNAseq data from various human developmental stages. Our implemented method identifies pseudo-perturbations, since actual perturbations are unavailable due to ethical and technical constraints. By integrating these pseudo-perturbations with prior knowledge of gene interactions, our framework generates stage-specific Boolean networks (BNs). We apply our method to medium and late trophectoderm developmental stages and identify 20 pseudo-perturbations required to infer BNs. The resulting BN families delineate distinct regulatory mechanisms, enabling the differentiation between these developmental stages. We show that our program outperforms existing pseudo-perturbation identification tool. Our framework contributes to comprehending human developmental processes and holds potential applicability to diverse developmental stages and other research scenarios.
单细胞转录组学研究分化系统可以进行有意义的理解,特别是在人类胚胎发育和细胞命运决定方面。我们提出了一种创新方法,旨在通过利用来自不同人类发育阶段的 scRNAseq 数据来模拟这些复杂的过程。我们实施的方法可以识别伪扰动,因为由于伦理和技术限制,实际上无法进行扰动。通过将这些伪扰动与基因相互作用的先验知识相结合,我们的框架生成了特定于阶段的布尔网络(BN)。我们将该方法应用于中晚期滋养外胚层发育阶段,并确定了推断 BN 所需的 20 个伪扰动。由此产生的 BN 家族划定了不同的调控机制,能够区分这些发育阶段。我们表明,我们的程序优于现有的伪扰动识别工具。我们的框架有助于理解人类发育过程,并且具有在不同发育阶段和其他研究场景中应用的潜力。