Angarita-Rodríguez Andrea, Mendoza-Mejía Nicolás, González Janneth, Papin Jason, Aristizábal Andrés Felipe, Pinzón Andrés
Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá, Colombia.
Laboratorio de Bioinformática y Biología de Sistemas, Universidad Nacional de Colombia Bogotá, Bogotá, Colombia.
Front Syst Biol. 2025 Jan 3;4:1500710. doi: 10.3389/fsysb.2024.1500710. eCollection 2024.
The availability of large-scale multi-omic data has revolution-ized the study of cellular machinery, enabling a systematic understanding of biological processes. However, the integration of these datasets into Genome-Scale Models of Metabolism (GEMs) re-mains underexplored. Existing methods often link transcriptome and proteome data independently to reaction boundaries, providing models with estimated maximum reaction rates based on individual datasets. This independent approach, however, introduces uncertainties and inaccuracies.
To address these challenges, we applied a principal component analysis (PCA)-based approach to integrate transcriptome and proteome data. This method facilitates the reconstruction of context-specific models grounded in multi-omics data, enhancing their biological relevance and predictive capacity.
Using this approach, we successfully reconstructed an astrocyte GEM with improved prediction capabilities compared to state-of-the-art models available in the literature.
These advancements underscore the potential of multi-omic inte-gration to refine metabolic modeling and its critical role in studying neurodegeneration and developing effective therapies.
大规模多组学数据的可用性彻底改变了细胞机制的研究,使人们能够系统地理解生物过程。然而,将这些数据集整合到基因组规模代谢模型(GEMs)中仍未得到充分探索。现有方法通常将转录组和蛋白质组数据独立地链接到反应边界,为模型提供基于单个数据集的估计最大反应速率。然而,这种独立的方法会引入不确定性和不准确性。
为应对这些挑战,我们应用了一种基于主成分分析(PCA)的方法来整合转录组和蛋白质组数据。该方法有助于基于多组学数据重建特定背景模型,增强其生物学相关性和预测能力。
使用这种方法,我们成功重建了一个星形胶质细胞GEM,与文献中现有的最先进模型相比,其预测能力有所提高。
这些进展凸显了多组学整合在完善代谢建模方面的潜力及其在研究神经退行性变和开发有效疗法中的关键作用。