Distinguishing different modes of growth using single-cell data

Author:

Kar Prathitha12ORCID,Tiruvadi-Krishnan Sriram3,Männik Jaana3ORCID,Männik Jaan3ORCID,Amir Ariel1ORCID

Affiliation:

1. Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University

2. Department of Chemistry and Chemical Biology, Harvard University

3. Department of Physics and Astronomy, University of Tennessee

Abstract

Collection of high-throughput data has become prevalent in biology. Large datasets allow the use of statistical constructs such as binning and linear regression to quantify relationships between variables and hypothesize underlying biological mechanisms based on it. We discuss several such examples in relation to single-cell data and cellular growth. In particular, we show instances where what appears to be ordinary use of these statistical methods leads to incorrect conclusions such as growth being non-exponential as opposed to exponential and vice versa. We propose that the data analysis and its interpretation should be done in the context of a generative model, if possible. In this way, the statistical methods can be validated either analytically or against synthetic data generated via the use of the model, leading to a consistent method for inferring biological mechanisms from data. On applying the validated methods of data analysis to infer cellular growth on our experimental data, we find the growth of length in E. coli to be non-exponential. Our analysis shows that in the later stages of the cell cycle the growth rate is faster than exponential.

Funder

US-Israel BSF Research Grant

National Institutes of Health

National Science Foundation

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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