University of Washington, Seattle, 98195-5065, USA.
Brief Bioinform. 2012 Nov;13(6):769-80. doi: 10.1093/bib/bbs022. Epub 2012 May 15.
The human microbiome is a complex biological system with numerous interacting components across multiple organizational levels. The assembly, ecology and dynamics of the microbiome and its contribution to the development, physiology and nutrition of the host are clearly affected not only by the set of genes or species in the microbiome but also by the way these genes are linked across numerous pathways and by the interactions between the various species. To date, however, most studies of the human microbiome have focused on characterizing the composition of the microbiome and on comparative analyses, whereas significantly less effort has been directed at elucidating, characterizing and modeling these interactions and on studying the microbiome as a complex, interconnected and cohesive system. Here, specifically, I highlight the pressing need for the development of predictive system-level models and for a system-level understanding of the microbiome, and discuss potential computational frameworks for metagenomic-based modeling of the microbiome at the cellular, ecological and supra-organismal level. I review some preliminary attempts at constructing such models and examine the challenges and hurdles that such modeling efforts face. I also discuss possible future applications and research avenues that such metagenomic systems biology and predictive system-level models may facilitate.
人类微生物组是一个复杂的生物系统，具有多个相互作用的组件，跨越多个组织层次。微生物组的组装、生态学和动态及其对宿主的发育、生理学和营养的贡献不仅受到微生物组中基因或物种的集合的影响，而且还受到这些基因在众多途径中的连接方式以及各种物种之间的相互作用的影响。然而，迄今为止，大多数人类微生物组的研究都集中在描述微生物组的组成和比较分析上，而对阐明、描述和建模这些相互作用以及将微生物组作为一个复杂、相互关联和有凝聚力的系统进行研究的努力则明显较少。在这里，我特别强调迫切需要开发预测系统级模型和对微生物组的系统级理解，并讨论基于宏基因组学的细胞、生态和超生物体水平微生物组建模的潜在计算框架。我回顾了一些构建此类模型的初步尝试，并研究了此类建模工作所面临的挑战和障碍。我还讨论了这种宏基因组系统生物学和预测系统级模型可能带来的可能的未来应用和研究途径。
