Cell-free prediction of protein expression costs for growing cells

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Abstract

Translating heterologous proteins places significant burden on host cells, consuming expression resources leading to slower cell growth and productivity. Yet predicting the cost of protein production for any given gene is a major challenge, as multiple processes and factors combine to determine translation efficiency. To enable prediction of the cost of gene expression in bacteria, we describe here a standard cell-free lysate assay that provides a relative measure of resource consumption when a protein coding sequence is expressed. These lysate measurements can then be used with a computational model of translation to predict the in vivo burden placed on growing E. coli cells for a variety of proteins of different functions and lengths. Using this approach, we can predict the burden of expressing multigene operons of different designs and differentiate between the fraction of burden related to gene expression compared to action of a metabolic pathway.

Article activity feed

  1. SciScore for 10.1101/172627: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    No key resources detected.


    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).


    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.


    Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).


    Results from JetFighter: Please consider improving the colormap used on pages 9, 28, 29 and 30. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.


    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore is not a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by drawing attention to sections of the manuscript that contain or should contain various rigor criteria and key resources. For details on the results shown here, including references cited, please follow this link.

  2. SciScore for 10.1101/172627: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    No key resources detected.


    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).


    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.


    Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).


    Results from JetFighter: Please consider improving the colormap used on pages 9, 28, 29 and 30. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.


    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore is not a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by drawing attention to sections of the manuscript that contain or should contain various rigor criteria and key resources. For details on the results shown here, including references cited, please follow this link.

  3. SciScore for 10.1101/172627: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

      <p><b>Table 1: Rigor</b></p>
      <i>NIH rigor criteria are not applicable to paper type.</i>
      <p><b>Table 2: Resources</b></p>
      <p><i>No key resources detected.</i></p>
      
      <hr><p><i>Results from OddPub</i>: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see <a href="http://blogs.nature.com/naturejobs/2017/06/19/ask-not-what-you-can-do-for-open-data-ask-what-open-data-can-do-for-you/">Nature blog</a>).</p><hr style="border-top: 1px solid #ccc;"><p><i>Results from LimitationRecognizer</i>: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.</p><hr style="border-top: 1px solid #ccc;"><p><i>Results from Barzooka</i>: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).</p><hr style="border-top: 1px solid #ccc;"><p><i>Results from JetFighter</i>: Please consider improving the colormap used on pages 9, 28, 29 and 30. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.</p><hr><p><b>About SciScore</b></p>
      <p>SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore is not
      a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research
      resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore
      also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences
      that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria
      that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by
      drawing attention to sections of the manuscript that contain or should contain various rigor criteria and
      key resources. For details on the results shown here, including references cited, please follow <a href="https://docs.google.com/document/d/1fY0Uze8b4udlPGDLNfAXgFiXzxUeACLssA_lieKMqTI/edit">this link</a>.
    
  4. SciScore for 10.1101/172627: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

      <p><b>Table 1: Rigor</b></p>
      <i>NIH rigor criteria are not applicable to paper type.</i>
      <p><b>Table 2: Resources</b></p>
      <p><i>No key resources detected.</i></p>
      
      <hr><p><i>Results from OddPub</i>: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see <a href="http://blogs.nature.com/naturejobs/2017/06/19/ask-not-what-you-can-do-for-open-data-ask-what-open-data-can-do-for-you/">Nature blog</a>).</p><hr style="border-top: 1px solid #ccc;"><p><i>Results from LimitationRecognizer</i>: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.</p><hr style="border-top: 1px solid #ccc;"><p><i>Results from Barzooka</i>: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).</p><hr style="border-top: 1px solid #ccc;"><p><i>Results from JetFighter</i>: Please consider improving the colormap used on pages 9, 28, 29 and 30. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.</p><hr><p><b>About SciScore</b></p>
      <p>SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore is not
      a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research
      resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore
      also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences
      that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria
      that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by
      drawing attention to sections of the manuscript that contain or should contain various rigor criteria and
      key resources. For details on the results shown here, including references cited, please follow <a href="https://docs.google.com/document/d/1fY0Uze8b4udlPGDLNfAXgFiXzxUeACLssA_lieKMqTI/edit">this link</a>.
    
  5. SciScore for 10.1101/172627: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

      <p><b>Table 1: Rigor</b></p>
      <i>NIH rigor criteria are not applicable to paper type.</i>
      <p><b>Table 2: Resources</b></p>
      <p><i>No key resources detected.</i></p>
      
      <hr><p><i>Results from OddPub</i>: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see <a href="http://blogs.nature.com/naturejobs/2017/06/19/ask-not-what-you-can-do-for-open-data-ask-what-open-data-can-do-for-you/">Nature blog</a>).</p><hr style="border-top: 1px solid #ccc;"><p><i>Results from LimitationRecognizer</i>: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.</p><hr style="border-top: 1px solid #ccc;"><p><i>Results from Barzooka</i>: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).</p><hr style="border-top: 1px solid #ccc;"><p><i>Results from JetFighter</i>: Please consider improving the colormap used on pages 9, 28, 29 and 30. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.</p><hr><p><b>About SciScore</b></p>
      <p>SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore is not
      a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research
      resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore
      also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences
      that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria
      that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by
      drawing attention to sections of the manuscript that contain or should contain various rigor criteria and
      key resources. For details on the results shown here, including references cited, please follow <a href="https://docs.google.com/document/d/1fY0Uze8b4udlPGDLNfAXgFiXzxUeACLssA_lieKMqTI/edit">this link</a>.
    
  6. SciScore for 10.1101/172627: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

      <p><b>Table 1: Rigor</b></p>
      <i>NIH rigor criteria are not applicable to paper type.</i>
      <p><b>Table 2: Resources</b></p>
      <p><i>No key resources detected.</i></p>
      
      <hr><p><i>Results from OddPub</i>: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see <a href="http://blogs.nature.com/naturejobs/2017/06/19/ask-not-what-you-can-do-for-open-data-ask-what-open-data-can-do-for-you/">Nature blog</a>).</p><hr style="border-top: 1px solid #ccc;"><p><i>Results from LimitationRecognizer</i>: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.</p><hr style="border-top: 1px solid #ccc;"><p><i>Results from Barzooka</i>: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).</p><hr style="border-top: 1px solid #ccc;"><p><i>Results from JetFighter</i>: Please consider improving the colormap used on pages 9, 28, 29 and 30. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.</p><hr><p><b>About SciScore</b></p>
      <p>SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore is not
      a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research
      resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore
      also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences
      that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria
      that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by
      drawing attention to sections of the manuscript that contain or should contain various rigor criteria and
      key resources. For details on the results shown here, including references cited, please follow <a href="https://docs.google.com/document/d/1fY0Uze8b4udlPGDLNfAXgFiXzxUeACLssA_lieKMqTI/edit">this link</a>.
    
  7. SciScore for 10.1101/172627: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

      <p><b>Table 1: Rigor</b></p>
      <i>NIH rigor criteria are not applicable to paper type.</i>
      <p><b>Table 2: Resources</b></p>
      <p><i>No key resources detected.</i></p>
      
      <hr><p><i>Results from OddPub</i>: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see <a href="http://blogs.nature.com/naturejobs/2017/06/19/ask-not-what-you-can-do-for-open-data-ask-what-open-data-can-do-for-you/">Nature blog</a>).</p><hr style="border-top: 1px solid #ccc;"><p><i>Results from LimitationRecognizer</i>: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.</p><hr style="border-top: 1px solid #ccc;"><p><i>Results from Barzooka</i>: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).</p><hr style="border-top: 1px solid #ccc;"><p><i>Results from JetFighter</i>: Please consider improving the colormap used on pages 9, 28, 29 and 30. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.</p><hr><p><b>About SciScore</b></p>
      <p>SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore is not
      a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research
      resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore
      also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences
      that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria
      that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by
      drawing attention to sections of the manuscript that contain or should contain various rigor criteria and
      key resources. For details on the results shown here, including references cited, please follow <a href="https://docs.google.com/document/d/1fY0Uze8b4udlPGDLNfAXgFiXzxUeACLssA_lieKMqTI/edit">this link</a>.