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Predictive analytics of environmental adaptability in multi-omic network models

机译:多组网模型中环境适应性的预测分析

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摘要

Bacterial phenotypic traits and lifestyles in response to diverse environmental conditions depend on changes in the internal molecular environment. However, predicting bacterial adaptability is still difficult outside of laboratory controlled conditions. Many molecular levels can contribute to the adaptation to a changing environment: pathway structure, codon usage, metabolism. To measure adaptability to changing environmental conditions and over time, we develop a multi-omic model of Escherichia coli that accounts for metabolism, gene expression and codon usage at both transcription and translation levels. After the integration of multiple omics into the model, we propose a multiobjective optimization algorithm to find the allowable and optimal metabolic phenotypes through concurrent maximization or minimization of multiple metabolic markers. In the condition space, we propose Pareto hypervolume and spectral analysis as estimators of short term multi-omic (transcriptomic and metabolic) evolution, thus enabling comparative analysis of metabolic conditions. We therefore compare, evaluate and cluster different experimental conditions, models and bacterial strains according to their metabolic response in a multidimensional objective space, rather than in the original space of microarray data. We finally validate our methods on a phenomics dataset of growth conditions. Our framework, named METRADE, is freely available as a MATLAB toolbox.
机译:应对不同环境条件的细菌表型特征和生活方式取决于内部分子环境的变化。但是,在实验室控制的条件之外,仍然很难预测细菌的适应性。许多分子水平可有助于适应不断变化的环境:途径结构,密码子使用,新陈代谢。为了衡量适应不断变化的环境条件并随时间推移的适应性,我们开发了一种多基因组大肠杆菌模型,该模型考虑了转录和翻译水平上的代谢,基因表达和密码子使用情况。在将多个组学整合到模型中之后,我们提出了一种多目标优化算法,以通过同时最大化或最小化多个代谢标记物来找到允许的最佳代谢表型。在条件空间中,我们提出帕累托超量和光谱分析作为短期多基因组(转录组和代谢)进化的估计量,从而能够对代谢条件进行比较分析。因此,我们在多维目标空间而不是在微阵列数据的原始空间中,根据它们的代谢反应对不同的实验条件,模型和细菌菌株进行比较,评估和聚类。最后,我们在生长条件的表型学数据集上验证了我们的方法。我们的名为METRADE的框架可作为MATLAB工具箱免费获得。

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