Peer Review History

Original SubmissionMarch 28, 2024
Decision Letter - Rocco Franco, Editor

PONE-D-24-12205Method for Predicting Parkinson's Disease through Differential Gut MicrobiotaPLOS ONE

Dear Dr. 张,

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.

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ACADEMIC EDITOR:

Please change this manuscript according the reviewer's recommendation. 

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Please submit your revised manuscript by Jun 22 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're 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.

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). You should upload this letter as a separate file labeled 'Response to Reviewers'.
  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Rocco Franco

Academic Editor

PLOS ONE

Journal requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. Please provide a complete Data Availability Statement in the submission form, ensuring you include all necessary access information or a reason for why you are unable to make your data freely accessible. If your research concerns only data provided within your submission, please write "All data are in the manuscript and/or supporting information files" as your Data Availability Statement.

Additional Editor Comments:

Please adjust this paper according the reviewer's recommendation.

Regards

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

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: I Don't Know

Reviewer #2: N/A

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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: The study has Good design and a novel study but the study involves human specimens and requires an Ethical clearance. Authors have not discussed the results of their study in the "Discussion" section properly. They need to elaborate the discussion to compare and focus their results.

Reviewer #2: Thank you for allowing me to review the manuscript titled: Method for Predicting Parkinson's Disease through Differential Gut Microbiota. The manuscript is well-written, and the research work is of high quality.

I have a few comments:

1. Title: The current title needs to be less generalized and should provide readers with an idea of the actual content of the manuscript. As the study focuses on developing a Deep learning tool, it is advised to add some words related to Deep learning in the title to make it more interesting and specific

2. Materials and methods:

a)Secton 2.3 “In that study, a method for predicting Parkinson's disease patients using differential microbiota was implemented.” : Please quote the study and cite the reference

b)“The overall framework of the PGPM method constructed in that article was illustrated in Figure 1,”: Please quote the study and cite the reference

c)Section 2.5 .“ LSIM In that study, the classifier for the MDOS method was based on a combined classification strategy of LSTM-SVM” : Please quote the study and cite the reference

d)Provide details about who performed the annotation of deep learning tool.

e)How was blinding performed to avoid bias?

f)“ This experiment conducted comparative trials across multiple models, with identical hyperparameter settings as follows: the number of training epochs was set to 300, the initial learning rate was set at 0.001, the batch size was set to 6,” : please cite the reference and

g)“optimization algorithm used was Adaptive Moment Estimation (Adam)” : Provide details of company and Version of the software

3. Discussion: “ Bedarf et al. reported found significant differences in the composition of the gut microbiota between Parkinson's disease patients and healthy controls” : please cite the reference

4. Discussion can be elaborated as its too short.

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6. 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 #1: Yes: Sumir Gandhi

Reviewer #2: No

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[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.]

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 PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Revision 1

Response to Reviewer 1:

Dear Sumir Gandhi:

We greatly appreciate your positive feedback on our research and the issues you pointed out in this systematic review and meta-analysis. Based on your suggestions, we have made the relevant corrections in the document and have addressed your comments:

Comment1:The study has Good design and a novel study but the study involves human specimens and requires an Ethical clearance. Authors have not discussed the results of their study in the "Discussion" section properly. They need to elaborate the discussion to compare and focus their results.

Response: We greatly appreciate you pointing out this issue. This study, which involves human participants, has been reviewed and approved by the Ethics Committee of Xiangyang First People's Hospital. Written informed consent was obtained from the patients/participants for their participation in this study. Additionally, we have made the revisions you suggested to the discussion section of the manuscript and marked these changes accordingly.

Dear Reviewer 2:

Dear Reviewer:

We greatly appreciate your positive feedback on our study and the issues you pointed out in this systematic review and meta-analysis. Based on your suggestions, we have made the necessary corrections in the document and have addressed your comments accordingly.

Comment 1:The current title needs to be less generalized and should provide readers with an idea of the actual content of the manuscript. As the study focuses on developing a Deep learning tool, it is advised to add some words related to Deep learning in the title to make it more interesting and specific.

Response1:Thank you very much for pointing out this issue. We have revised the title of the study to include the term "deep learning." The revised title is " Deep Learning-based Differential Gut Flora for Prediction of Parkinson's"

Comment a:Secton 2.3 “In that study, a method for predicting Parkinson's disease patients using differential microbiota was implemented.” : Please quote the study and cite the reference.

Response a:Thank you very much for pointing out this issue, and we apologize for the confusion. Due to our writing error, "In this study" was mistakenly written as "In that study," causing misunderstanding. The method mentioned is the one used in our current study, and there is no external reference to cite.

Comment b:“The overall framework of the PGPM method constructed in that article was illustrated in Figure 1,”: Please quote the study and cite the reference.

Response b: Thank you very much for pointing out this issue. It may have been a mistake in our writing that caused the misunderstanding. The PGPM method is the name of the method used in our current study, and it cannot be referenced to external literature.

Comment c:Section 2.5 .“ LSIM In that study, the classifier for the MDOS method was based on a combined classification strategy of LSTM-SVM” : Please quote the study and cite the reference.

Response c: Thank you very much for pointing out this issue. We apologize for the confusion caused by our writing error where "MDOS" was mistakenly used. It has been corrected to "PGPM" method, and therefore, there is no reference to cite. We sincerely apologize for any misunderstanding caused.

Comment d: Provide details about who performed the annotation of deep learning tool.

Response d: Thank you very much for pointing out the issue. This study was implemented in Python (version 3.9.12) using publicly available standard libraries, including pandas (version 1.5.2), numpy (version 1.22.4), scikit-learn (version 1.2.0), torch (version 1.12), and matplotlib (version 3.6.2). We have also added this information to the manuscript.

Comment e: How was blinding performed to avoid bias?

Response e: Thank you very much for pointing out this issue. In this study, the data were collected from Parkinson's patients and their healthy spouses in the same region, with a gender ratio of 1:1. During the experiments, we utilized the DataLoader method to randomly shuffle the sample order in the dataset at the beginning of each epoch to avoid bias.

Comment f: This experiment conducted comparative trials across multiple models, with identical hyperparameter settings as follows: the number of training epochs was set to 300, the initial learning rate was set at 0.001, the batch size was set to 6,” : please cite the reference.

Response f: Thank you very much for pointing out this issue. We have added references to the manuscript as suggested. However, some of the parameters are based on our experimental experience and thus cannot be referenced.

Comment g:“optimization algorithm used was Adaptive Moment Estimation (Adam)” : Provide details of company and Version of the software.

Response g:Thank you very much for pointing out this issue. The GPU used for training in this study is the NVIDIA GeForce GTX1060 laptop GPU, with 16GB of memory and 1280 CUDA cores. We have already added this information to the manuscript.

Comment 3:Discussion: “ Bedarf et al. reported found significant differences in the composition of the gut microbiota between Parkinson's disease patients and healthy controls” : please cite the reference.

Response 3:Thank you very much for pointing out the issue. We have now added the citation of the reference at this location.

Comment 4:Discussion can be elaborated as its too short.

Comment 4:Thank you very much for bringing up this issue. We have addressed the problem of the "Discussion" section being too brief as you pointed out, and we have made the necessary revisions, which are now indicated in the manuscript.

Attachments
Attachment
Submitted filename: Response to Reviewers.docx
Decision Letter - Rocco Franco, Editor

PONE-D-24-12205R1Deep Learning-based Differential Gut Flora for Prediction of Parkinson'sPLOS ONE

Dear Dr. 张,

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. 

Please submit your revised manuscript by Aug 10 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're 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.

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). You should upload this letter as a separate file labeled 'Response to Reviewers'.
  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.
If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Rocco Franco

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments:

Dear Authors,

Please follow the reviewer recommendation

Regards

[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 #1: All comments have been addressed

Reviewer #2: All comments have been addressed

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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 #1: Yes

Reviewer #2: Yes

**********

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

Reviewer #1: I Don't Know

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 #1: Yes

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 #1: Yes

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 #1: The authors have made certain changes in the manuscript. But cupola of points still need to be addressed--

1. Specify aims and objective of the study.

2. I discussion section, authors have focussed in the predictive model but not on their results. Please elaborate on that.

Reviewer #2: All comments were answered well and necessary change were made in the manuscript. I believe the manuscript can be accepted in the present from.

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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 #1: Yes: Sumir Gandhi

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.]

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 PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Revision 2

Response to Reviewer 1:

Dear Professor Sumir Gandhi:

We greatly appreciate your positive feedback on our research and the issues you pointed out in this systematic review and meta-analysis. Based on your suggestions, we have made the relevant corrections in the document and have addressed your comments:

Comment1:Specify aims and objective of the study.

Response1: We greatly appreciate you pointing out this issue. The core objective of this study is to develop an efficient and accurate prediction method for the early diagnosis of Parkinson's disease through an in-depth analysis of gut microbiota data. We propose a differential gut microbiota-based Parkinson's prediction method (PGPM) based on deep learning, aiming to capture the subtle differences in the gut microbiome that traditional statistical methods may miss, offering new perspectives and tools for Parkinson's disease prediction. Additionally, we have incorporated the study's aims and objectives into the abstract and introduction sections and highlighted them in red. Thank you again for pointing out this issue.

Comment2:I discussion section, authors have focussed in the predictive model but not on their results. Please elaborate on that.

Response2: We greatly appreciate you pointing out this issue. We have realized that the discussion section was overly focused on our model while neglecting our results. We have made revisions to the original text, adding a section on the results of our study to the discussion. Thank you again for your guidance on our research.

Response to Reviewer 2:

Dear reviewers2:

It is a great honour to have your approval of this work.

Attachments
Attachment
Submitted filename: Response to Reviewers.docx
Formally Accepted
Acceptance Letter - Upaka Rathnayake, Editor

PONE-D-24-12205R2

PLOS ONE

Dear Dr. Zhang,

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Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Professor Upaka Rathnayake

Academic Editor

PLOS ONE

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