State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, 32, Eastern Jiaochang Road, Kunming, Yunnan 650223, China.
Biochem Biophys Res Commun. 2011 Nov 25;415(3):450-4. doi: 10.1016/j.bbrc.2011.10.090. Epub 2011 Oct 25.
The availability and utility of genome-scale metabolic networks have exploded with modern genome-sequencing capabilities. However, these generic models overlooked actual physiological states of the tissues and included all the reactions implied by the genome annotations. To address this problem, we reconstructed a human heart-specific metabolic network based on transcriptome and proteome data. The resulting model consists of 2803 reactions and 1880 metabolites, which correspond to 1721 active enzymes in human heart. Using the model, we detected 24 epistatic interactions in human heart, which are useful in understanding both the structure and function of cardiovascular systems. In addition, a set of 776 potential biomarkers for cardiovascular disease (CVD) has been successfully explored, whose concentration is predicted to be either elevated or reduced because of 278 possible dysfunctional cardiovascular-associated genes. The model could also be applied in predicting selective drug targets for eight subtypes of CVD. The human heart-specific model provides valuable information for the studies of cardiac activity and development of CVD.
随着现代基因组测序能力的提高，基因组规模的代谢网络的可用性和实用性呈爆炸式增长。然而，这些通用模型忽略了组织的实际生理状态，包含了基因组注释中暗示的所有反应。为了解决这个问题，我们基于转录组和蛋白质组数据重建了一个人类心脏特异性代谢网络。该模型由 2803 个反应和 1880 种代谢物组成，对应于人类心脏中 1721 种活跃的酶。使用该模型，我们在人类心脏中检测到 24 个上位相互作用，这些相互作用有助于理解心血管系统的结构和功能。此外，还成功地探索了一组 776 种心血管疾病 (CVD) 的潜在生物标志物，由于 278 种可能存在功能障碍的心血管相关基因，其浓度预计会升高或降低。该模型还可用于预测 CVD 八种亚型的选择性药物靶点。该人类心脏特异性模型为心脏活动和 CVD 的研究提供了有价值的信息。
