PONE-D-21-23106

Identification of key genes and immune infiltration modulated by CPAP in Obstructive sleep apnea by integrated bioinformatics analysis

PLOS ONE

Dear Dr. Song,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, 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 Sep 26 2021 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: http://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,

Giannicola Iannella

Academic Editor

PLOS ONE

Journal Requirements:

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

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. In your Data Availability statement, you have not specified where the minimal data set underlying the results described in your manuscript can be found. PLOS defines a study's minimal data set as the underlying data used to reach the conclusions drawn in the manuscript and any additional data required to replicate the reported study findings in their entirety. All PLOS journals require that the minimal data set be made fully available. For more information about our data policy, please see http://journals.plos.org/plosone/s/data-availability.

"Upon re-submitting your revised manuscript, please upload your study’s minimal underlying data set as either Supporting Information files or to a stable, public repository and include the relevant URLs, DOIs, or accession numbers within your revised cover letter. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. Any potentially identifying patient information must be fully anonymized.

Important: If there are ethical or legal restrictions to sharing your data publicly, please explain these restrictions in detail. Please see our guidelines for more information on what we consider unacceptable restrictions to publicly sharing data: http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. Note that it is not acceptable for the authors to be the sole named individuals responsible for ensuring data access.

We will update your Data Availability statement to reflect the information you provide in your cover letter.

3. 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

4.Please include your full ethics statement in the ‘Methods’ section of your manuscript file. In your statement, please include the full name of the IRB or ethics committee who approved or waived your study, as well as whether or not you obtained informed written or verbal consent. If consent was waived for your study, please include this information in your statement as well. 

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. 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: No

**********

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: Abstract

line 2, the sentencens are separated by a point. Please unify.

Background

- page 2, line 1, same of abstract line 2. Please unify the sentences.

- after line 1 add: The direct consequence of the intermittent hypoxia is an oxidative imbalance, with reactive oxygen species production, inflammatory cytokines (IL2, IL4, IL6), lipid peroxidation, and cell-free DNA production and please cite doi:10.3390/jcm10020277

- line 5, describe the findings of the study cited [5].

- line 7, add: however CPAP treatment could fail in patients with lingual tonsil hypertrophy and TORS could represent a valid therapeutic option for retrolingual airway collapse. please cite doi:10.1002/rcs.2106

- line ''Furthermore, immune cells infiltration was evaluated in OSA patients via CIBERSORT, and correlations between key genes and immune cells infiltration were calculated. '' Introduce first why you calculated immune infiltration and if there are studies that correlate it mention them in the text.

Materials and methods

describe the study design, year, protocol and cite a flow diagram to explain all the protocol with selection criteria.

Results

interesting and well written

Discussion

Line 1, cite papers on CPAP role in OSAS treatment discussing the main findings: doi:10.1007/s11325-014-1097-3

doi:10.1007/s11325-016-1419-8

- [11] please check the font

- '''Others have not been reported to have closely relationship with immunity.'' please cite the papers that states what you affirmed

Reviewer #2: The authors interestingly analyzed OSAS related genes correlating the outcomes with CPAP treatment. The paper has scientific soundness; however, minor corrections are required.

- English editing is necessary for both grammatic and punctuation (.And, patten, time‐ consuming);

Abstract

- before the sentence ''in conclusion.. report briefly the results found.

Background

- CPAP is not to date the only possible treatment in patients with obstructive sleep apnea. Different new technologies have been developed according to the profiles of the obstruction sites identified at Drug Induced Sleep Endoscopy, including different techniques from barbed wire pharyngoplasty up to robotic surgery in retrolingual collapses. Please cite doi: 10.1002 / rcs.2106 and doi: 10.1007 / s00405-020-05883-2

- please clarify the study protocol with a figure or a flowchart describing all the procedures performed;

Discussion

- cite references that support what stated in the sentence: ''The core genes of the clinically significant modules were supposed to be important in the remission of OSA''

the same with the sentence: '' Others have not been reported to have closely relationship with immunity. ...

- please read this review and modify the concept. In reality different biomarkers have been demonstrated in the literature: '' However, there are no related reports whether these genes can be used as therapeutic efficacy biomarkers of OSA. ''

- please read these metaanalysis and modify the concept. In reality different biomarkers have been demonstrated in the literature: '' However, there are no related reports whether these genes can be used as therapeutic efficacy biomarkers of OSA. ''

Imani MM, Sadeghi M, Khazaie H, Emami M, Sadeghi Bahmani D, Brand S. Evaluation of Serum and Plasma Interleukin-6 Levels in Obstructive Sleep Apnea Syndrome: A Meta-Analysis and Meta-Regression. Front Immunol. 2020 Jul 21; 11: 1343. doi: 10.3389 / fimmu.2020.01343. PMID: 32793188; PMCID: PMC7385225. and the paper

Rezaei F, Abbasi H, Sadeghi M, Imani MM. The effect of obstructive sleep apnea syndrome on serum S100B and NSE levels: a systematic review and meta-analysis of observational studies. BMC Pulm Med. 2020 Feb 5; 20 (1): 31. doi: 10.1186 / s12890-020-1063-8. PMID: 32024492; PMCID: PMC7003338.

- discuss at the end study's limitation

**********

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

Identification of key genes and immune infiltration modulated by CPAP in Obstructive sleep apnea by integrated bioinformatics analysis

PONE-D-21-23106R1

Dear Dr. Song,

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 for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. 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 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,

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

very interesting study.

The authors well replay to the comments of the reviewers. I believe that this paper is suitable of publication on PLOS ONE.

Best regards

Reviewers' comments:

-