Diversified Control Paths: A Significant Way Disease Genes Perturb the Human Regulatory Network.
Diversified Control Paths: A Significant Way Disease Genes Perturb the Human Regulatory Network.
复制标题
多样化的控制途径：疾病基因扰乱人类调节网络的重要方式
DOI：
10.1371/journal.pone.0135491
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Guo X
中科院分区：
文献类型：
--
作者：
Wang B;Gao L;Zhang Q;Li A;Deng Y;Guo X
背景生物系统的复杂性促使我们利用潜在的网络来深入理解疾病的病因，而人类疾病被视为网络动态特性的扰动。处理动态系统的控制理论已经成功地用于捕获大量定量生物相互作用中的系统级知识。但从系统控制的角度来看，多种遗传因素共同干扰疾病表型的方式仍然存在。结果本文将控制理论和网络科学的联合收割机工具相结合，解决了复杂网络中多样化的控制路径问题。然后，疾病基因扰乱生物系统的方式被识别和量化的控制路径在人类调节网络。此外，作为一个应用程序，优先级的候选基因的控制路径分析和基因本体标注的相似性定义。我们使用留一交叉验证来评估发现基因-疾病关系的能力。结果表明，兼容性能与以前的复杂的作品，特别是在定向系统。结论我们的结果激发了对驱动病理过程的分子机制的更深入理解。多样化的控制途径为综合干预技术提供了基础，这将最终导致新的治疗策略的发展。
Background The complexity of biological systems motivates us to use the underlying networks to provide deep understanding of disease etiology and the human diseases are viewed as perturbations of dynamic properties of networks. Control theory that deals with dynamic systems has been successfully used to capture systems-level knowledge in large amount of quantitative biological interactions. But from the perspective of system control, the ways by which multiple genetic factors jointly perturb a disease phenotype still remain. Results In this work, we combine tools from control theory and network science to address the diversified control paths in complex networks. Then the ways by which the disease genes perturb biological systems are identified and quantified by the control paths in a human regulatory network. Furthermore, as an application, prioritization of candidate genes is presented by use of control path analysis and gene ontology annotation for definition of similarities. We use leave-one-out cross-validation to evaluate the ability of finding the gene-disease relationship. Results have shown compatible performance with previous sophisticated works, especially in directed systems. Conclusions Our results inspire a deeper understanding of molecular mechanisms that drive pathological processes. Diversified control paths offer a basis for integrated intervention techniques which will ultimately lead to the development of novel therapeutic strategies.
影响因子：
3
作者：
Küntzer J;Backes C;Blum T;Gerasch A;Kaufmann M;Kohlbacher O;Lenhof HP
通讯作者：
Lenhof HP