Eng Alexander, Borenstein Elhanan
Department of Genome Sciences.
Department of Genome Sciences Department of Computer Science and Engineering, University of Washington, Seattle, WA, USA Santa Fe Institute, Santa Fe, NM, USA.
Bioinformatics. 2016 Jul 1;32(13):2008-16. doi: 10.1093/bioinformatics/btw107. Epub 2016 Feb 26.
Recent efforts to manipulate various microbial communities, such as fecal microbiota transplant and bioreactor systems' optimization, suggest a promising route for microbial community engineering with numerous medical, environmental and industrial applications. However, such applications are currently restricted in scale and often rely on mimicking or enhancing natural communities, calling for the development of tools for designing synthetic communities with specific, tailored, desired metabolic capacities.
Here, we present a first step toward this goal, introducing a novel algorithm for identifying minimal sets of microbial species that collectively provide the enzymatic capacity required to synthesize a set of desired target product metabolites from a predefined set of available substrates. Our method integrates a graph theoretic representation of network flow with the set cover problem in an integer linear programming (ILP) framework to simultaneously identify possible metabolic paths from substrates to products while minimizing the number of species required to catalyze these metabolic reactions. We apply our algorithm to successfully identify minimal communities both in a set of simple toy problems and in more complex, realistic settings, and to investigate metabolic capacities in the gut microbiome. Our framework adds to the growing toolset for supporting informed microbial community engineering and for ultimately realizing the full potential of such engineering efforts.
The algorithm source code, compilation, usage instructions and examples are available under a non-commercial research use only license at https://github.com/borenstein-lab/CoMiDA CONTACT: elbo@uw.edu
Supplementary data are available at Bioinformatics online.
近期对各种微生物群落进行调控的努力,如粪便微生物群移植和生物反应器系统优化,为微生物群落工程提供了一条前景广阔的途径,具有众多医学、环境和工业应用。然而,此类应用目前在规模上受到限制,且往往依赖于模仿或增强自然群落,因此需要开发工具来设计具有特定、定制化所需代谢能力的合成群落。
在此,我们朝着这一目标迈出了第一步,引入了一种新颖的算法,用于识别微生物物种的最小集合,这些物种共同提供从一组预定义的可用底物合成一组所需目标产物代谢物所需的酶促能力。我们的方法在整数线性规划(ILP)框架中将网络流的图论表示与集合覆盖问题相结合,以同时识别从底物到产物的可能代谢途径,同时最小化催化这些代谢反应所需的物种数量。我们将算法应用于成功识别一组简单的玩具问题以及更复杂、现实场景中的最小群落,并研究肠道微生物群中的代谢能力。我们的框架为支持明智的微生物群落工程以及最终实现此类工程努力的全部潜力增加了越来越多的工具集。
该算法的源代码、编译、使用说明和示例可在https://github.com/borenstein-lab/CoMiDA上仅在非商业研究使用许可下获取。联系方式:elbo@uw.edu
补充数据可在《生物信息学》在线获取。