Hawe Johann S, Theis Fabian J, Heinig Matthias
Institute of Computational Biology, HelmholtzZentrum München, Munich, Germany.
Department of Informatics, Technische Universität München, Munich, Germany.
Front Genet. 2019 Jun 12;10:535. doi: 10.3389/fgene.2019.00535. eCollection 2019.
A major goal in systems biology is a comprehensive description of the entirety of all complex interactions between different types of biomolecules-also referred to as the interactome-and how these interactions give rise to higher, cellular and organism level functions or diseases. Numerous efforts have been undertaken to define such interactomes experimentally, for example yeast-two-hybrid based protein-protein interaction networks or ChIP-seq based protein-DNA interactions for individual proteins. To complement these direct measurements, genome-scale quantitative multi-omics data (transcriptomics, proteomics, metabolomics, etc.) enable researchers to predict novel functional interactions between molecular species. Moreover, these data allow to distinguish relevant functional from non-functional interactions in specific biological contexts. However, integration of multi-omics data is not straight forward due to their heterogeneity. Numerous methods for the inference of interaction networks from homogeneous functional data exist, but with the advent of large-scale paired multi-omics data a new class of methods for inferring comprehensive networks across different molecular species began to emerge. Here we review state-of-the-art techniques for inferring the topology of interaction networks from functional multi-omics data, encompassing graphical models with multiple node types and quantitative-trait-loci (QTL) based approaches. In addition, we will discuss Bayesian aspects of network inference, which allow for leveraging already established biological information such as known protein-protein or protein-DNA interactions, to guide the inference process.
系统生物学的一个主要目标是全面描述不同类型生物分子之间所有复杂的相互作用(也称为相互作用组),以及这些相互作用如何产生更高层次的细胞和生物体水平的功能或疾病。人们已经进行了大量努力,通过实验来定义这样的相互作用组,例如基于酵母双杂交的蛋白质 - 蛋白质相互作用网络或基于ChIP - seq的单个蛋白质的蛋白质 - DNA相互作用。为了补充这些直接测量,基因组规模的定量多组学数据(转录组学、蛋白质组学、代谢组学等)使研究人员能够预测分子物种之间新的功能相互作用。此外,这些数据能够在特定生物学背景下区分相关的功能相互作用和非功能相互作用。然而,由于多组学数据的异质性,整合这些数据并非易事。存在许多从同质功能数据推断相互作用网络的方法,但随着大规模配对多组学数据的出现,一类用于推断跨不同分子物种的综合网络的新方法开始出现。在这里,我们回顾了从功能多组学数据推断相互作用网络拓扑结构的最新技术,包括具有多种节点类型的图形模型和基于数量性状位点(QTL)的方法。此外,我们将讨论网络推断的贝叶斯方面,它允许利用已建立的生物学信息,如已知的蛋白质 - 蛋白质或蛋白质 - DNA相互作用,来指导推断过程。