A Bayesian non-parametric mixed-effects model of microbial growth curves

被引:11
|
作者
Tonner, Peter D. [1 ,2 ,7 ]
Darnell, Cynthia L. [2 ]
Bushell, Francesca M. L. [3 ]
Lund, Peter A. [3 ]
Schmid, Amy K. [1 ,2 ,4 ]
Schmidler, Scott C. [1 ,5 ,6 ]
机构
[1] Duke Univ, Program Computat Biol & Bioinformat, Durham, NC 27708 USA
[2] Duke Univ, Biol Dept, Durham, NC 27708 USA
[3] Univ Birmingham, Inst Microbiol & Infect, Sch Biosci, Birmingham, W Midlands, England
[4] Duke Univ, Ctr Computat Biol & Bioinformat, Durham, NC 27708 USA
[5] Duke Univ, Dept Stat Sci, Durham, NC USA
[6] Duke Univ, Dept Comp Sci, Durham, NC 27708 USA
[7] NIST, Gaithersburg, MD 20899 USA
基金
英国生物技术与生命科学研究理事会; 美国国家科学基金会;
关键词
HETEROGENEOUS HEAT RESPONSE; STRAIN VARIABILITY; ESCHERICHIA-COLI; OXIDATIVE STRESS; BACTERIAL; CONSEQUENCES; INACTIVATION; UNCERTAINTY; EXPRESSION; PHYSIOLOGY;
D O I
10.1371/journal.pcbi.1008366
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Substantive changes in gene expression, metabolism, and the proteome are manifested in overall changes in microbial population growth. Quantifying how microbes grow is therefore fundamental to areas such as genetics, bioengineering, and food safety. Traditional parametric growth curve models capture the population growth behavior through a set of summarizing parameters. However, estimation of these parameters from data is confounded by random effects such as experimental variability, batch effects or differences in experimental material. A systematic statistical method to identify and correct for such confounding effects in population growth data is not currently available. Further, our previous work has demonstrated that parametric models are insufficient to explain and predict microbial response under non-standard growth conditions. Here we develop a hierarchical Bayesian non-parametric model of population growth that identifies the latent growth behavior and response to perturbation, while simultaneously correcting for random effects in the data. This model enables more accurate estimates of the biological effect of interest, while better accounting for the uncertainty due to technical variation. Additionally, modeling hierarchical variation provides estimates of the relative impact of various confounding effects on measured population growth.
引用
收藏
页数:21
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