PONE-D-23-26444Identification of crucial genes and functional network features of leprosy based on GEO expression profilesPLOS ONE

Dear Dr. Zheng,

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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Study examines the several crucial gene markers and related important pathways that acted as essential components in the etiology of leprosy, which may enhance our fundamental knowledge of immune molecular mechanisms underlying the initiation and development of leprosy. Leprosy has a high rate of cripplehood and lacks available early effective diagnosis methods for prevention and treatmen .

Article is excellent for the translational perspective, presented in an intelligible fashion and written in standard english however, technical, statistical explanation required extensively for the better understanding of the article. Article should refer latest studies in same field and refer its clinical relevance.

I had appended the reviewer comment for the better understanding and to make article in better shape.

Decision- Major revision with response to all reviewers comment pointwise.

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We look forward to receiving your revised manuscript.

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Anshuman Mishra, PhD

Academic Editor

PLOS ONE

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Additional Editor Comments:

Study entitled- Identification of crucial genes and functional network features of leprosy based on GEO expression profiles by Y Zheng el al 2023.

Dear Dr. Zheng,

Study examines the several crucial gene markers and related important pathways that acted as essential components in the etiology of leprosy, which may enhance our fundamental knowledge of immune molecular mechanisms underlying the initiation and development of leprosy. Leprosy has a high rate of cripplehood and lacks available early effective diagnosis methods for prevention and treatmen .

Article is excellent for the translational perspective, presented in an intelligible fashion and written in standard english however, technical, statistical explanation required extensively for the better understanding of the article. Article should refer latest studies in same field and refer its clinical relevance.

I had appended the reviewer comment for the better understanding and to make article in better shape.

Decision- Major revision with response to all reviewers comment pointwise.

Reviewers' comments:

[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

Reviewer #3: Yes

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

Reviewer #1: Yes

Reviewer #2: I Don't Know

Reviewer #3: 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

Reviewer #3: 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: No

Reviewer #3: 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: This paper presents results from a pipeline of analyses using various R packages. The analyses of publicly available microarray data from GEO repository found 49 crucial genes associated with leprosy susceptibility. These 49 genes were both differentially expressed and hub genes of WGCNA.

For reproducibility's sake, I think, it'd be good if the authors make their R codes used for all analysis publicly available.

Reviewer #2: This manuscript utilizes large-data and bioinformatics techniques to assess relationships and associations between pathophysiology of leprosy and gene/molecular markers. This study aims to provide insight into the pathogenesis of leprosy and identify potential biomarkers that may be implemented as therapeutic targets in the future. The authors implement WCGNA, DEG, and PPI analyses to identify a network of genes predominantly related to immune regulation that may play a role in the pathogenesis and pathophysiology of leprosy.

Major comments:

1. Please explain why the cutoffs and threshold limits (e.g. cutoffs for GS and MM, threshold for WGCNA analysis) were selected, including if similar studies implemented the same cutoffs.

2. Please provide more explanation as to how the statistics were performed beyond the R package(s) utilized. Notably, the supplementary datasets contain statistical values that should be transferred to some capacity into the main text.

3. Verbiage that was used to describe findings should be revised (e.g. revising “we got a gene-pathway network” to “we identified…”; “10 genes were finally got”, etc.)

Minor comments:

1. Please provide more explanation and description of the methods, including how/why each database was utilized.

Overall, this is a study that provides insight into the pathogenesis of leprosy using bioinformatics techniques. However, there are several critical considerations that require attention.

Reviewer #3: Identification of crucial genes and functional network features of leprosy based on GEO expression profiles

Here the authors have collected the bioinformatics analysis with leprosy and normal samples using GEO database. They have screened 85 hub genes using WGCNA. They performed DEG analysis and screened 82 up-regulated and 3 down-regulated genes. Finally, they have identified 10 genes (ITK, CD48, IL2RG, CCR5, FGR, JAK3, STAT1, LCK, PTPRC, CXCR4). They have suggested these 10 genes can be used as leprosy Biomarker because they were active in 6 immune system pathways, including Chemokine signaling pathway, Th1 and Th2 cell differentiation, Th17 cell differentiation, T cell receptor signalling pathway, Natural killer cell mediated cytotoxicity and Leukocyte trans endothelial migration. The research is exciting and valuable enough to be published in PLoS One. Before being accepted for publication, the piece must, however, be appropriately revised in accordance with the remarks offered below.

Comments:

1. The title of the manuscript should be modified.

2. If possible graphical abstract should be provided. According to journal format if it is not possible in the main text, it can be provided in the supplementary file for better understanding of the readers (optional).

3. The Abstract portion should be modified.

4. Line Numbers should be added throughout manuscript.

5. The introduction portion should be rewritten.

6. The author should give a strong hypothesis why this study in details.

7. Introduction section:

(3rd Paragraph) Line no -1: detecte should be corrected.

8. Materials and method section:

Here the authors have simply written they have taken the data and have used the different softwares for the data analysis but the detailed analysis regarding how it is doing that is completely lacking. This should be addressed properly.

9. Results section:

All figures need a better resolution. The author should also mention the image source and the software used to make the images.

10. Conclusion section:

The conclusion portion should be rewritten and the author must add a paragraph on future prospects

11. After the conclusion section there should be some small sections like: Supporting information, Acknowledgments, Author Contributions etc

12. Correct the PubMed ID of Reference No. 40.

Recommendation: Major Revision

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

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Attachments

Attachment

Submitted filename: Bibhu_Review_ 25.10.2023.docx

PONE-D-23-26444R1Identification of Potential Biomarkers of Leprosy: A Study Based on GEO DatasetsPLOS ONE

Dear Dr. Zheng,

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.

Article is now in shape however needs further efforts to clinical relevance of study in discussion section. Comparative data or evaluation with another studies may give better insight.

Additionally, future prospect with better scope, affected region, populations, policy and technology relevance will connect it for better healthcare management.

Please submit your revised manuscript by Mar 14 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,

Anshuman Mishra, PhD

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 Dr. Yi Zheng,

Thanks for the revision. Article is now in shape however needs further efforts to clinical relevance of study in discussion section. Comparative data or evaluation with another studies may give better insight.

Additionally, future prospect with better scope, affected region, populations, policy and technology relevance will connect it for better healthcare management.

[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 of Potential Biomarkers of Leprosy: A Study Based on GEO Datasets

PONE-D-23-26444R2

Dear Dr. Zheng,

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.

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Kind regards,

Anshuman Mishra, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: