Fibroblast-specific genome-scale modelling predicts an imbalance in amino acid metabolism in Refsum disease. Fibroblast-specific genome-scale modelling predicts an imbalance in amino acid metabolism in Refsum disease

In this study, we reconstructed a fibroblast-specific genome-scale model based on the recently published, FAD-curated model, based on Recon3D reconstruction. To constrain the model we used transcriptomics, and proteomics data, which we obtained from healthy controls and Refsum disease patient fibroblasts incubated with phytol, a precursor of phytanic acid. Using this model, we investigated the metabolic phenotype of Refsum disease at the genome-scale, and we studied the effect of phytanic acid on cell metabolism. We identified 20 metabolites that were predicted to discriminate between Healthy and Refsum disease patients, several of which with a link to amino acid metabolism. Overall design: Comparison between control and Refsum disease patient cell lines (and models) metabolism, with or without exposure to phytol.

本研究以近期发表的、经FAD整理并基于Recon3D重构的模型为基础，构建了成纤维细胞特异性基因组规模代谢模型。为约束该模型参数，我们使用了从健康对照成纤维细胞与经植烷醇（phytol，植烷酸的前体物质）孵育的雷夫叙姆病（Refsum disease）患者成纤维细胞中获取的转录组学与蛋白质组学数据。依托该模型，我们在基因组规模层面解析了雷夫叙姆病的代谢表型，并探究了植烷酸（phytanic acid）对细胞代谢的影响。我们共鉴定出20种可用于区分健康个体与雷夫叙姆病患者的代谢物，其中多种与氨基酸代谢存在关联。实验整体设计：对比暴露与未暴露于植烷醇的健康对照与雷夫叙姆病患者细胞系（及对应模型）的代谢特征。