Joint BSC-IRB Program in Computational Biology, Institute for Research in Biomedicine, Barcelona, Spain.
PLoS One. 2012;7(2):e31220. doi: 10.1371/journal.pone.0031220. Epub 2012 Feb 21.
Genome sequencing projects provide nearly complete lists of the individual components present in an organism, but reveal little about how they work together. Follow-up initiatives have deciphered thousands of dynamic and context-dependent interrelationships between gene products that need to be analyzed with novel bioinformatics approaches able to capture their complex emerging properties. Here, we present a novel framework for the alignment and comparative analysis of biological networks of arbitrary topology. Our strategy includes the prediction of likely conserved interactions, based on evolutionary distances, to counter the high number of missing interactions in the current interactome networks, and a fast assessment of the statistical significance of individual alignment solutions, which vastly increases its performance with respect to existing tools. Finally, we illustrate the biological significance of the results through the identification of novel complex components and potential cases of cross-talk between pathways and alternative signaling routes.
基因组测序项目提供了生物体中存在的各个组件的近乎完整的列表,但几乎没有揭示它们如何协同工作。后续的计划已经破解了数千个基因产物之间的动态和上下文相关的相互关系,需要使用新型的生物信息学方法来分析这些相互关系,这些方法能够捕捉到它们复杂的新兴特性。在这里,我们提出了一种新的框架,用于对齐和比较任意拓扑结构的生物网络。我们的策略包括基于进化距离预测可能保守的相互作用,以应对当前相互作用网络中大量缺失的相互作用,并快速评估单个对齐解决方案的统计显著性,这极大地提高了其相对于现有工具的性能。最后,我们通过识别新的复杂成分和途径之间以及替代信号通路之间可能的串扰的潜在情况,说明了结果的生物学意义。