School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Bioinformatics. 2010 Jun 15;26(12):i228-36. doi: 10.1093/bioinformatics/btq197.
Genetic interactions between genes reflect functional relationships caused by a wide range of molecular mechanisms. Large-scale genetic interaction assays lead to a wealth of information about the functional relations between genes. However, the vast number of observed interactions, along with experimental noise, makes the interpretation of such assays a major challenge.
Here, we introduce a computational approach to organize genetic interactions and show that the bulk of observed interactions can be organized in a hierarchy of modules. Revealing this organization enables insights into the function of cellular machineries and highlights global properties of interaction maps. To gain further insight into the nature of these interactions, we integrated data from genetic screens under a wide range of conditions to reveal that more than a third of observed aggravating (i.e. synthetic sick/lethal) interactions are unidirectional, where one gene can buffer the effects of perturbing another gene but not vice versa. Furthermore, most modules of genes that have multiple aggravating interactions were found to be involved in such unidirectional interactions. We demonstrate that the identification of external stimuli that mimic the effect of specific gene knockouts provides insights into the role of individual modules in maintaining cellular integrity.
We designed a freely accessible web tool that includes all our findings, and is specifically intended to allow effective browsing of our results (http://compbio.cs.huji.ac.il/GIAnalysis).
Supplementary data are available at Bioinformatics online.
基因之间的遗传相互作用反映了由广泛的分子机制引起的功能关系。大规模的遗传相互作用实验导致了大量关于基因之间功能关系的信息。然而，大量观察到的相互作用，以及实验噪声，使得解释这些实验成为一个主要挑战。
在这里，我们介绍了一种组织遗传相互作用的计算方法，并表明大量观察到的相互作用可以在模块层次结构中进行组织。揭示这种组织可以深入了解细胞机制的功能，并突出交互映射的全局属性。为了进一步了解这些相互作用的性质，我们整合了来自广泛条件下遗传筛选的数据，揭示了超过三分之一的观察到的加重（即合成病/致死）相互作用是单向的，其中一个基因可以缓冲另一个基因干扰的影响，但反之则不行。此外，发现具有多个加重相互作用的大多数基因模块都参与了这种单向相互作用。我们证明，识别模拟特定基因敲除效果的外部刺激，可以深入了解单个模块在维持细胞完整性中的作用。
我们设计了一个免费的网络工具，其中包含了我们所有的发现，特别是旨在允许有效地浏览我们的结果（http://compbio.cs.huji.ac.il/GIAnalysis）。
补充数据可在生物信息学在线获得。
