PONE-D-23-39620Identification the hub genes of periodontitis and diabetes by bioinformatics and experimentPLOS ONE

Dear Dr. luo,

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 Mar 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,

Qi Zhao

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.  Thank you for stating the following financial disclosure: 

"This research was supported by Taizhou Science and Technology planning Project (NO. 20ywb67)."

Please state what role the funders took in the study.  If the funders had no role, please state: "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript." 

If this statement is not correct you must amend it as needed. 

Please include this amended Role of Funder statement in your cover letter; we will change the online submission form on your behalf.

3. 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.

4. PLOS requires an ORCID iD for the corresponding author in Editorial Manager on papers submitted after December 6th, 2016. Please ensure that you have an ORCID iD and that it is validated in Editorial Manager. To do this, go to ‘Update my Information’ (in the upper left-hand corner of the main menu), and click on the Fetch/Validate link next to the ORCID field. This will take you to the ORCID site and allow you to create a new iD or authenticate a pre-existing iD in Editorial Manager. Please see the following video for instructions on linking an ORCID iD to your Editorial Manager account: https://www.youtube.com/watch?v=_xcclfuvtxQ

5. Please remove your figures from within your manuscript file, leaving only the individual TIFF/EPS image files, uploaded separately. These will be automatically included in the reviewers’ PDF.

6. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information. 

[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

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

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

**********

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: No

Reviewer #2: Yes

**********

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: 1.English expressions need to be edited more careful and more native, in this manuscript, there are some mistakes. For example, there is no period in the last sentence in method of the abstract.

2. I suggest the authors should add a flowchart in the manuscript to show the process very well.

3. I suggest the authors should elaborate their motivation in the discussion section, as they use several common bioinformatics analysis methods and online tools. What is the novelty and technicality of their work?

4.The advancement of interaction prediction research in various fields of computational biology would provide valuable insights into genetic markers and ncRNAs related with DM, such as miRNA-lncRNA interaction prediction. The authors should discuss it as the future direction. Important computational models in these fields should be cited. Some recommended studies are helpful (PMIDs: 36642414, 36924730, 36305458, 34232474, 37525507, 37660567 and 37466194).

5. The authors should carefully check and unify the information of references. Some references lack the information of volume or contain the wrong page number.

6. Literature review is incomplete in the introduction, especially about the research of differentially expressed genes (DEGs) involvement in periodontitis by computational tools or bioinformatic analysis. I suggest the authors to discuss the recent updates in the related field. Different feature weight calculation methods within a single algorithm result in divergent rankings of DEGs. I think we need consistency and comparable results.

7. Materials and methods section is relatively simple because of no detail about the analysis. The analysis methods and statistical parameters must be clearly emphasized (i.e, reasons for selecting the algorithms used, threshold values used in statistical analysis, etc.).

Reviewer #2: 1.What do “LPS” and “LAPTM5, RAC2, LYN”represent in the Abstract section? What are their full names? When first mentioned, the author should provide their full names to help readers better understand.

2.The authors should add a flowchart in the manuscript to show the process very well.

3.The description of the result is quite simple and too short, especially the descriptions of “Identification of Common DEGs” and “The analysis of immune infiltration”. The authors should add some necessary sentences to describe these results.

4.The labeling of Figures in the paper is quite small. The contents within the figures are unclear. The author needs to carefully revise and modify the figure.

5.The discussion of the deficiencies in current research is quite poor. The authors should discuss it as the future direction. ODE-based theoretical modeling studies on gene/protein signaling networks have been equally important for the study of understanding regulatory mechanisms and finding potential therapeutic targets in diseases (PMID: 35958114, https://doi.org/10.1016/j.chaos.2023.114328, and https://doi.org/10.1103/PhysRevE.108.064412). Would it be possible to discuss and cite these studies in conjunction with the conclusions of this paper?

6.Besides, the advancement of interaction prediction research in various fields of computational biology would provide valuable insights into genetic markers and related diseases. Important computational models in these fields should be discussed and cited. Some recommended studies are helpful (PMIDs: 36584603, 35817399, 36305458).

7.The authors should carefully check and unify the information of references. Some references lack the information of page number, such as refs [7] and [30].

**********

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: 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.]

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.

PONE-D-23-39620R1Identification the hub genes of periodontitis and diabetes by bioinformatics and experimentPLOS ONE

Dear Dr. luo,

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 May 05 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,

Qi Zhao

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.

[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: (No Response)

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 #1: Yes

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

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: 1.The workflow in supplementary material is unspecific and less organized. It's more like a stack of terminologies than a higher-level summary of the existing data and methodologies, please improve it. And this figure should be moved to the main body of revised manuscript.

2. The authors have already addressed most of the issues raised by the reviewer. But there are still some grammatical errors in the article, and the expression of some of the content is not clear enough. The authors need to check the manuscript carefully and make corresponding revision.

3. The authors should revise carefully corresponding to my previous comment #4. All the related paper should be cited.

Reviewer #2: The authors have addressed all the issues raised by the reviewer and can be accepted for publication in Plos one.

**********

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: 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.]

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.

PONE-D-23-39620R2Identification the hub genes of periodontitis and diabetes by bioinformatics and experimentPLOS ONE

Dear Dr. luo,

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 Jan 09 2025 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,

Simin Li, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments:

Dear Dr. Rong Luo,

Thank you for submitting your revised manuscript "Identification the hub genes of periodontitis and diabetes by bioinformatics and experiment" (PONE-D-23-39620R2) to PLOS ONE. We have now received comments from reviewers regarding your revised submission, and I am writing to inform you that your manuscript requires further major revisions before it can be considered for publication.

While we acknowledge the improvements made in this revision, there are still significant concerns that need to be addressed. We have received contrasting recommendations from our reviewers, with one suggesting rejection and another recommending major revision. After careful evaluation of both reviews, I believe that your manuscript shows promise but requires substantial improvements to meet PLOS ONE's publication criteria.

When preparing your next revision, please provide a comprehensive response to all reviewer comments, ensuring that any changes are clearly highlighted in the manuscript. Please ensure that your conclusions are fully supported by your data and that all statistical analyses are appropriate and clearly described.

Please note that your revised version will be sent back to the reviewers for further assessment of how well you have addressed their concerns. We believe that carefully addressing these issues will significantly strengthen your paper and increase its potential impact in the field.

Please submit your revised manuscript within 30 days. If you anticipate any delay, please let us know your expected resubmission date by replying to this email.

We look forward to receiving your revised manuscript.

Best regards,

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 #1: All comments have been addressed

Reviewer #3: All comments have been addressed

Reviewer #4: (No Response)

Reviewer #5: 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 #1: Yes

Reviewer #3: No

Reviewer #4: No

Reviewer #5: Yes

**********

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

Reviewer #1: Yes

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: 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 #3: (No Response)

Reviewer #4: Yes

Reviewer #5: 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 #3: No

Reviewer #4: Yes

Reviewer #5: 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 author has already addressed all of the issues. I think the manuscript can be published in PLOS ONE.

Reviewer #3:  Thank you to the authors for the considerable amount of work done in the study "Identification of the hub genes of periodontitis and diabetes by bioinformatics and experiment," as well as for addressing some of the reviewers' comments during the revision process. However, from my personal perspective, I find it difficult to agree with the authors' results and conclusions. The main reasons are as follows:

The authors used the dataset GSE7014, which includes 10 DM1 biopsies, 20 DM2 biopsies, and 6 normal individuals' biopsies of skeletal muscle. The GSE16134 database includes a total of 120 patients undergoing periodontal surgery, each contributing with a minimum of two interproximal gingival papillae. This results in two major flaws for the study.

Firstly, Type 1 diabetes and Type 2 diabetes are diseases with completely different genetic and pathological mechanisms, making it entirely unacceptable to combine them. Secondly, there is a significant difference in gene expression between the interproximal gingival papillae and skeletal muscle tissues in the two datasets. Therefore, I regret to say that I cannot agree with your analysis results and conclusions.

Reviewer #4:  The manuscript titled "Identification of the hub genes of periodontitis and diabetes by bioinformatics and experiment" addresses an interesting intersection between periodontitis and diabetes mellitus, suggesting that shared molecular mechanisms could be explored via bioinformatics to identify key genes (LAPTM5, RAC2, and LYN). While the authors have provided a detailed bioinformatic analysis and experimental validation, there are significant concerns regarding the novelty and depth of the study:

The idea of identifying shared pathways between periodontitis and diabetes using bioinformatics is not entirely novel. Similar studies exist that delve into shared molecular mechanisms and immune responses in various diseases, including periodontitis and diabetes. The manuscript does not adequately highlight how its findings significantly advance the existing body of knowledge beyond what has been previously published.

While the study follows a well-known bioinformatic pipeline (DEGs identification, functional analysis, and protein-protein interaction network), it lacks innovation in methodology. The application of widely-used datasets (e.g., GSE7014 and GSE16134) without integrating more recent or diverse datasets from single-cell RNA sequencing (scRNA-seq) or other omics approaches limits the potential impact of the findings.

Furthermore, the study's use of in vitro validation, while helpful, does not explore functional assays beyond qPCR, and the validation itself remains quite basic.

The study relies on standard bioinformatic tools, but statistical robustness should be further scrutinized. For example, the selection of hub genes might benefit from additional cross-validation or more advanced machine learning techniques, which would add weight to the findings.

The authors have not integrated the latest available data on single-cell RNA sequencing for periodontitis or diabetes. Recent studies have shown the value of scRNA-seq in understanding cellular heterogeneity in diseases. The omission of these newer datasets weakens the study's relevance in the current scientific landscape.

Given these limitations, I would recommend rejecting the paper at this stage. The manuscript could benefit from incorporating more novel datasets, improving statistical validation, and considering recent developments in the field such as scRNA-seq for a more comprehensive analysis. Additionally, a more thorough discussion of how the results compare to and advance the current understanding of periodontitis-diabetes interactions would be necessary for future revisions.

Reviewer #5:  The manuscript, "Identification of the hub genes of periodontitis and diabetes by bioinformatics and experiment," has undergone thorough revisions, and I appreciate the authors' efforts in addressing the reviewers' feedback meticulously. The modifications significantly enhance the clarity and rigor of the study, particularly with the added flowchart, detailed descriptions of the methods and results, and improved figure readability. The authors have also provided a well-structured discussion, including the proposed future directions and acknowledgment of research limitations, making the study more robust. Moreover, the inclusion of computational models and ODE-based theoretical modeling studies as references aligns well with the study's objectives and brings additional depth to the discussion.

**********

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: No

Reviewer #3: No

Reviewer #4: No

Reviewer #5: Yes:  Shixiong Wei

**********

[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.

Identification the hub genes of periodontitis and diabetes by bioinformatics and experiment

PONE-D-23-39620R3

Dear Dr. Luo,

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

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager®  and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, 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 help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- 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.

Kind regards,

Xiaozhe Han, D.M.D., Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Thanks for all the efforts to improve the manuscript. It is better organized now and contains new information to be shared with relative scientific community.

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 #4: 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 #1: Yes

Reviewer #4: Yes

**********

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

Reviewer #1: Yes

Reviewer #4: 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 #4: 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 #4: 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 necessary revisions and has greatly improved the manuscript. I have no further comments.

Reviewer #4: I reviewed the manuscript carefully. The authors performed the revision properly. I have no further comments.

**********

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: No

Reviewer #4: Yes:  Yun Hak Kim

**********