Peer Review History

Original SubmissionJuly 8, 2019
Decision Letter - Ram Chandra Bajpai, Editor

PONE-D-19-18970

SiZer Map to investigate significant features of body-weight profile changes in HIV infected patients in the IeDEA Collaboration

PLOS ONE

Dear Dr. Yiannoutsos,

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We look forward to receiving your revised manuscript.

Kind regards,

Ram Chandra Bajpai, Ph.D.

Academic Editor

PLOS ONE

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5. Thank you for stating the following in the Acknowledgments Section of your manuscript:

[Data collection was funded by the NIH National Institute of Allergies and Infectious

Diseases (NIAID). Samiha Sarwat was supported in part by Grant Number TL1 TR000162 (A.

Shekhar, PI) from the National Institutes of Health, National Center for Advancing Translational

Sciences, Clinical and Translational Sciences Award]

We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form.

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The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript and no funds were directly provided to any of the authors.]

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[The authors have declared that no competing interests exist.].   

* We note that one or more of the authors are employed by a commercial company: 'Bayer U.S., LLC'.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: In this manuscript, the authors presented an improved method for SiZer, PS-SiZer, which aims at increasing sensitivity and accuracy in detecting relevant features. On simulated data, PS-SiZer has better sensitivity than existing methods. On real data, PS-SiZer can find useful features and biological inferences can be made through these features. The manuscript will be good for publication if the authors solve the following issues:

1. In Table 1, the authors show that PS-SiZer detect a much higher fraction of features than the other two methods. In Figure 2, the authors show that PS-SiZer can detect all features in the simulated study. In Figure 3, the estimated time to reach the plateau is much smaller in PS-SiZer than in other two methods. Taking these results together, is PS-SiZer overly sensitive? If not, can the authors perform another simulation to prove that?

2. The authors need to increase the resolution of figure 1a and 1b, and make figure 1c axis ticks bigger. There are also some typos, e.g. in page 10 "a family of smoonth".

Reviewer #2: Manuscript ID: PONE-D-19-18970

Title: SiZer Map to investigate significant features of body-weight profile changes in HIV infected patients in the IeDEA Collaboration

Summary:

The paper extends the method of SiZer maps to detect the time reaching a plateau when analyzing irregular longitudinal data by using penalized spline regression model (PS-SiZer).

Strengths:

1. It is nice to realize how the penalized spline regression model can be converted into the mixed-model framework to increase the computational efficiency.

2. Methodology development is well described from model specification, inference, estimate of first derivate, to confidence band.

3. Two simulation studies indicate better performance of PS-SiZer in detecting peaks and the time at peaks.

Comments:

1. Please clarify what Effective Degrees of Freedom (EDF) is and the purpose.

2. It is unclear how the model addresses the irregular longitudinal data.

3. The method section indicates the use of R package, mgcv::gam, as mixed model to estimate g(x) function, but data analysis used R package SiZer. Please clarify how g(x) function is estimated.

4. Is any difference of the proposed method vs “A Penalized Spline Approach to Functional Mixed Effects Model Analysis” by Chen and Wang (Biometrics, 2010)?

5. Please illustrate more how the optimum smoothing parameter is estimated using the ‘Rule of thumb’ approach.

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Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files to be viewed.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at figures@plos.org. Please note that Supporting Information files do not need this step.

Revision 1
Decision Letter - Ram Chandra Bajpai, Editor

PONE-D-19-18970R1

PS-SiZer Map to investigate significant features of body-weight profile changes in HIV infected patients in the IeDEA Collaboration

PLOS ONE

Dear Dr. Yiannoutsos,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Reviewer have highlighted that authors did not incorporate previous comments. Therefore, authors should clearly mention that how they have  incorporated those comments in the manuscript.

We would appreciate receiving your revised manuscript by Mar 16 2020 11:59PM. When you are ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.

To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). This letter should be uploaded as separate file and labeled 'Response to Reviewers'.
  • A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'.
  • An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'.

Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.

We look forward to receiving your revised manuscript.

Kind regards,

Ram Chandra Bajpai, Ph.D.

Academic Editor

PLOS ONE

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: (No Response)

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: The responses were not incorporated in the revised manuscript. Here is one example for illustration.

1. Please clarify what Effective Degrees of Freedom (EDF) is and the purpose.

Response: We have clarified that effective degrees of freedom encapsulate the complexity of the model as the actual degrees of freedom are not defined for the semiparametric models. We use the established method for their estimation, i.e. the trace of the smoother matrix (see Hastie & Tibshirani (1990) as cited in Chauduri & Marron (1999, pp. 812)).

The revised manuscript did not have any change to better explain EDF.

By making the SiZer maps comparable at a similar level of “Effective Degrees of Freedom” (EDF). For this reason all three SiZer maps (PS-SiZer with LL-SiZer and SS-SiZer) were generated with the same range of EDFs.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files to be viewed.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at figures@plos.org. Please note that Supporting Information files do not need this step.

Response to reviewers in attached file.

Regarding any conflict of interest of Dr. Sarwat, the work was completed during her doctoral research at Indiana University and prior to the commencement of her employment with Bayer. She has no conflicts and no commercial interests related to this work and this work is unrelated to her present employment.

As stated in the cover letter, we would like this manuscript to be considered for the special issue of Modeling in Infectious Diseases Call for Papers.

Attachments
Attachment
Submitted filename: PS-SiZer_ResponsesToTheReviewers.docx
Revision 2

The point about the EDFs is well taken and we apologize for having complicated the review. We have added the text into the body of the revised paper. To facilitate with identifying the changes made in the document, we have added comments in the margins where the precise response and the responded-to comment were identified.

Attachments
Attachment
Submitted filename: PS-SiZer_ResponsesToTheReviewers-with-clarification.docx
Decision Letter - Ram Chandra Bajpai, Editor

PS-SiZer Map to investigate significant features of body-weight profile changes in HIV infected patients in the IeDEA Collaboration

PONE-D-19-18970R2

Dear Dr. Yiannoutsos,

We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.

Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication.

Shortly after the formal acceptance letter is sent, an invoice for payment will follow. To ensure an efficient production and billing process, please log into Editorial Manager at https://www.editorialmanager.com/pone/, click the "Update My Information" link at the top of the page, and update your user information. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, you must inform our press team as soon as possible and no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

With kind regards,

Ram Chandra Bajpai, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: (No Response)

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: No

Formally Accepted
Acceptance Letter - Ram Chandra Bajpai, Editor

PONE-D-19-18970R2

PS-SiZer Map to investigate significant features of body-weight profile changes in HIV infected patients in the IeDEA Collaboration

Dear Dr. Yiannoutsos:

I am pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please notify them about your upcoming paper at this point, to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

For any other questions or concerns, please email plosone@plos.org.

Thank you for submitting your work to PLOS ONE.

With kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Ram Chandra Bajpai

Academic Editor

PLOS ONE

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