基于代谢网络拓扑特征的基因本质性预测

J. Nagai, H. Sousa, A. Aono, Ana Carolina Lorena, R. Kuroshu
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引用次数: 4

摘要

一些基本的问题,如什么基因对细胞的生存是真正必要的,激发了许多研究来调查不同物种基因的重要性。最初的努力试图通过在简单细菌中进行彻底的基因敲除实验来解决这个问题。最近,在这些研究中获得的结果也被应用于合成生物学的新兴领域,可能对许多其他领域产生影响,如卫生和能源。受DNA测序技术和高通量生物数据生成技术发展的推动,近年来人们在构建和理解生物网络方面也做出了许多努力。特别是,代谢网络代表了细胞内一系列已知的生化反应。必需基因预计在这些网络中发挥关键作用,因为它们必须参与重要的代谢途径。尽管一些研究调查了必需基因与生物网络信息的相关性,但通常将不同类型的网络和其他生物信息组合在一起,而不强调每种网络和其他生物信息在所得结果中的作用。本文描述了一种仅使用代谢网络的拓扑特征来预测必需基因的尝试。这些网络建立在一个共同的存储库——KEGG数据库之上,确保了数据的一致性。在实验中,考虑到不同的预测场景和参考生物,使用代谢网络的拓扑特征在预测基因必要性方面实现了约70%的平均AUC。这表明,更多的因素影响本质,确实应该考虑,以获得更准确的预测。
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Gene Essentiality Prediction Using Topological Features From Metabolic Networks
Fundamental questions such as what are the genes that are really necessary for the survival of cells have motivated many studies to investigate the essentiality of genes in different species. Initial efforts have attempted to address this problem through exhaustive knockout experiments in simple bacteria. Recently, results obtained in these studies have also been applied to the emerging field of synthetic biology with possible implications in many other fields such as health and energy. Motivated by the evolution of DNA sequencing technology and high-throughput biological data generation, many recent efforts have also been made for building and understanding biological networks. In particular, metabolic networks represent the set of known biochemical reactions within a cell. Essential genes are expected to play a key role in these networks, as they must be involved in vital metabolic pathways. Even though some studies investigated the correlation between essential genes and biological network information, different types of networks and other biological information were usually combined and the effect of each of them in the obtained results was not stressed. This paper describes an attempt to predict essential genes using solely topological features from metabolic networks. The networks were built from a common repository, the KEGG database, ensuring data uniformity. Experimentally, considering different prediction scenarios and reference organisms, the use of topological features from metabolic networks achieved mean AUC of about 70% in the prediction of gene essentiality. This reveals that more factors affect essentiality and should indeed be considered in order to obtain more accurate predictions.
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