Distinguishing different modes of growth using single-cell data

  1. Prathitha Kar
  2. Sriram Tiruvadi-Krishnan
  3. Jaana Männik
  4. Jaan Männik  Is a corresponding author
  5. Ariel Amir  Is a corresponding author
  1. Harvard University, United States
  2. University of Tennessee, United States

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.

Data availability

All data generated during this study are deposited in Dataverse-:Kar, Prathitha; Tiruvadi-Krishnan, Sriram; Männik, Jaana; Männik, Jaan; Amir, Ariel, 2021, "Distinguishing different modes of growth using single-cell data", https://doi.org/10.7910/DVN/BNQUDW, Harvard Dataverse, V1

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Prathitha Kar

    Department of Chemistry and Chemical Biology, Harvard University, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4091-6860
  2. Sriram Tiruvadi-Krishnan

    Department of Physics and Astronomy, University of Tennessee, Knoxville, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Jaana Männik

    Department of Physics and Astronomy, University of Tennessee, Knoxville, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Jaan Männik

    Department of Physics and Astronomy, University of Tennessee, Knoxville, United States
    For correspondence
    jmannik@utk.edu
    Competing interests
    The authors declare that no competing interests exist.
  5. Ariel Amir

    Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, United States
    For correspondence
    arielamir@seas.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2611-0139

Funding

US-Israel BSF Research Grant (2017004)

  • Jaan Männik

National Institutes of Health (R01GM127413)

  • Jaan Männik

National Science Foundation (NSF CAREER 1752024)

  • Ariel Amir

National Science Foundation (NSF award 1806818)

  • Prathitha Kar

National Institutes of Health (NIH grant 103346)

  • Prathitha Kar

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Gordon J Berman, Emory University, United States

Publication history

  1. Received: July 28, 2021
  2. Accepted: November 21, 2021
  3. Accepted Manuscript published: December 2, 2021 (version 1)
  4. Accepted Manuscript updated: December 8, 2021 (version 2)
  5. Version of Record published: January 4, 2022 (version 3)
  6. Version of Record updated: January 7, 2022 (version 4)

Copyright

© 2021, Kar et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 2,244
    Page views
  • 279
    Downloads
  • 4
    Citations

Article citation count generated by polling the highest count across the following sources: PubMed Central, Crossref, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Prathitha Kar
  2. Sriram Tiruvadi-Krishnan
  3. Jaana Männik
  4. Jaan Männik
  5. Ariel Amir
(2021)
Distinguishing different modes of growth using single-cell data
eLife 10:e72565.
https://doi.org/10.7554/eLife.72565

Further reading

    1. Microbiology and Infectious Disease
    Daan F van den Berg, Baltus A van der Steen ... Stan JJ Brouns
    Short Report

    tRNAs in bacteriophage genomes are widespread across bacterial host genera, but their exact function has remained unclear for more than 50 years. Several hypotheses have been proposed, and the most widely accepted one is codon compensation, which suggests that phages encode tRNAs that supplement codons that are less frequently used by the host. Here, we combine several observations and propose a new hypothesis that phage-encoded tRNAs counteract the tRNA-depleting strategies of the host using enzymes such as VapC, PrrC, Colicin D, and Colicin E5 to defend from viral infection. Based on mutational patterns of anticodon loops of tRNAs encoded by phages, we predict that these tRNAs are insensitive to host tRNAses. For phage-encoded tRNAs targeted in the anticodon itself, we observe that phages typically avoid encoding these tRNAs. Further supporting the hypothesis that phage tRNAs are selected to be insensitive to host anticodon nucleases. Altogether our results support the hypothesis that phage-encoded tRNAs have evolved to be insensitive to host anticodon nucleases.

    1. Microbiology and Infectious Disease
    Russell P Swift, Rubayet Elahi ... Sean T Prigge
    Research Article Updated

    Iron-sulfur clusters (FeS) are ancient and ubiquitous protein cofactors that play fundamental roles in many aspects of cell biology. These cofactors cannot be scavenged or trafficked within a cell and thus must be synthesized in any subcellular compartment where they are required. We examined the FeS synthesis proteins found in the relict plastid organelle, called the apicoplast, of the human malaria parasite Plasmodium falciparum. Using a chemical bypass method, we deleted four of the FeS pathway proteins involved in sulfur acquisition and cluster assembly and demonstrated that they are all essential for parasite survival. However, the effect that these deletions had on the apicoplast organelle differed. Deletion of the cysteine desulfurase SufS led to disruption of the apicoplast organelle and loss of the organellar genome, whereas the other deletions did not affect organelle maintenance. Ultimately, we discovered that the requirement of SufS for organelle maintenance is not driven by its role in FeS biosynthesis, but rather, by its function in generating sulfur for use by MnmA, a tRNA modifying enzyme that we localized to the apicoplast. Complementation of MnmA and SufS activity with a bacterial MnmA and its cognate cysteine desulfurase strongly suggests that the parasite SufS provides sulfur for both FeS biosynthesis and tRNA modification in the apicoplast. The dual role of parasite SufS is likely to be found in other plastid-containing organisms and highlights the central role of this enzyme in plastid biology.