Reconstruction and Validation of RefRec: A Global Model for the Yeast Molecular Interaction Network
Reconstruction and Validation of RefRec: A Global Model for the Yeast Molecular Interaction Network
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DOI：
10.1371/journal.pone.0010662
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发表时间：
2010-05-14
期刊：
影响因子：
3.7
通讯作者：
Yli-Harja, Olli
中科院分区：
文献类型：
--
作者：
Aho, Tommi;Almusa, Henrikki;Yli-Harja, Olli
分子相互作用网络建立了所有的细胞生物学过程。该网络正在进行深入研究，这是由新的高通量测量技术促进的，用于分子及其物理相互作用的检测、定量和表征。对于常见的模式生物酵母酿酒酵母，公共数据库存储了大量积累的信息，并且在更好地理解细胞过程的过程中，需要将这些信息整合到分子相互作用网络的一致重建中。这项工作提出并验证了RefRec，目前可用于酵母的最全面的分子相互作用网络重建。重建整合蛋白质合成途径，代谢网络，蛋白质-蛋白质相互作用网络从主要的生物数据库。重建的核心是基于参考对象的方法，其中基因，转录本和蛋白质使用其主要序列进行识别。这使得它们能够明确识别和非冗余集成。所获得的不同分子种类及其连接相互作用的总数近似于67，000。为了证明RefRec的功能预测能力，将其用于模拟分子相互作用网络中的基因敲除损伤传播，类似于590，000个实验验证的突变菌株。基于模拟结果，统计分类器随后能够正确地预测大多数菌株的活力。结果还表明，在重建中使用不同类型的分子物种是重要的，准确的表型预测。总的来说，研究结果证明了分子相互作用网络的全球重建的好处。所有的分子种类和它们的物理相互作用明确建模，我们的重建能够作为一个宝贵的资源，在额外的分析涉及对象从多个分子组。为此，RefRec以系统生物学标记语言格式免费提供。
Molecular interaction networks establish all cell biological processes. The networks are under intensive research that is facilitated by new high-throughput measurement techniques for the detection, quantification, and characterization of molecules and their physical interactions. For the common model organism yeast Saccharomyces cerevisiae, public databases store a significant part of the accumulated information and, on the way to better understanding of the cellular processes, there is a need to integrate this information into a consistent reconstruction of the molecular interaction network. This work presents and validates RefRec, the most comprehensive molecular interaction network reconstruction currently available for yeast. The reconstruction integrates protein synthesis pathways, a metabolic network, and a protein-protein interaction network from major biological databases. The core of the reconstruction is based on a reference object approach in which genes, transcripts, and proteins are identified using their primary sequences. This enables their unambiguous identification and non-redundant integration. The obtained total number of different molecular species and their connecting interactions is similar to 67,000. In order to demonstrate the capacity of RefRec for functional predictions, it was used for simulating the gene knockout damage propagation in the molecular interaction network in similar to 590,000 experimentally validated mutant strains. Based on the simulation results, a statistical classifier was subsequently able to correctly predict the viability of most of the strains. The results also showed that the usage of different types of molecular species in the reconstruction is important for accurate phenotype prediction. In general, the findings demonstrate the benefits of global reconstructions of molecular interaction networks. With all the molecular species and their physical interactions explicitly modeled, our reconstruction is able to serve as a valuable resource in additional analyses involving objects from multiple molecular -omes. For that purpose, RefRec is freely available in the Systems Biology Markup Language format.