PONE-D-21-21443

Gene signatures associated with barrier dysfunction and infection in oral lichen planus identified by meta-analysis of transcriptomic data

PLOS ONE

Dear Dr. Choi,

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Academic Editor

PLOS ONE

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“This study was supported by the National Research Foundation of Korea (Daejun, Korea) through the grants 2018R1A5A2024418 and 2020R1A2C2007038 awarded to Youngnim Choi and 2019R1A2C1002350 awarded to Sun Shim Choi.”

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Additional Editor Comments:

Although the reviewers found the study interesting, they have recommended to revise this manuscript in order to have more clarity in results. Also the reason to select IL-36G out of several overlapping DEGs identified needs to be addressed.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

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

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

Reviewer #1: Partly

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: 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: No

Reviewer #3: Yes

Reviewer #4: 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

Reviewer #3: Yes

Reviewer #4: 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: While going through the manuscript, I came through some lacking which have been addresses below:

1. I request the author to give logical and sound reasons for selection of IL-36G out of several overlapping DEGs identified. Out of two cytokines IL-36G and IL-1, author has chosen only IL-36G, I request to provide reason for selection of IL-36G.

2. Author is encouraged to provide the novelty of IL-36G to be used as a therapeutic target. I request to perform Receiver operating characteristic (ROC) analysis for IL-36G along with a reference marker.

Reviewer #2: The title:

- Meta-analysis may better describe an analysis of every single available transcriptomic dataset either microarray (which was done in this study) and RNA-seq data (which was not done in this study). Analysis of 2 datasets among the available ones may better be described by “analysis of transcriptomic data” instead of “meta-analysis.”

Line 57 (introduction):

- Liquefaction degeneration definition and characterization is missing specially it might be related to malignant transformation as mentioned in line 54 (PMID: 28556960).

Line 81 (methods):

- There are available public transcriptomic datasets such as GSE70665 (RNA-seq data). The present study is focusing on microarray data, so it might be better to skip mentioning the part that only 2 groups deposited their data as they their data as other data can be accessed in SRA format.

Line 98 (methods):

- “hclust function of the R package”: the package link is provided, but not the package name. It may be added “stats package in R”

Line 155 (figure 1 legend):

- It might be better to mention color change without gradual as the word gradual fits more for single cell transcriptomic data when a large number of cells is being plotted including cells during a transition state between the analysis conditions or when the data is a time-series one.

Line 156 (figure legend):

- It is very interesting that the authors marked the outliers in the heatmap (as you did) instead of plotting the final heatmap after removing outliers. Also, including how the downstream analysis resulted in no overlapping genes when all samples were included is very interesting.

Line 176 (results):

- Overlapping DEGs may need to be further described. Does it mean that the gene was found to be consistently upregulated or downregulated in both datasets OR the gene is considered to be overlapping if it was identified as a differentially expressed gene regardless the direction (upregulated or downregulated)? Was any genes found to be upregulated in a dataset and downregulated in the other dataset (bidirectional)? If yes, they should be mentioned. If no, that should be also mentioned.

Reviewer #3: Please re-check for minor grammatical inconsistency.

a) at line #134: please refine the header with a clear message of this result section

b) line 149: S2 Table-).

c) line #166: transcritomes should be transcriptomes

Reviewer #4: some minor concerns related to manuscript that needs to be addressed:

1. Why only IL-36G was chosen for validation at protein level while there were other potential candidate genes with higher fold change than IL-36G?

2. Authors should explain why the samples with other oral diseases such as chronic inflammation, acanthosis etc was chosen as controls in this study. Is it possible that the chronic inflammation in these control tissues are early signs of OLP?

3. IHC images needs to be labelled properly. It will help to emphasise the localisation of gene expression in specific cells or areas.

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Reviewer #1: No

Reviewer #2: Yes: Ahmed S Abouhashem

Reviewer #3: No

Reviewer #4: Yes: Renu Bala

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Gene signatures associated with barrier dysfunction and infection in oral lichen planus identified by analysis of transcriptomic data

PONE-D-21-21443R1

Dear Dr. Choi,

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.

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Kind regards,

Kanhaiya Singh, Ph.D

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

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

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

Reviewer #4: 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

Reviewer #4: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: 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 #2: 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 #2: 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: While reviewing the manuscript I found that all the suggestions have been beautifully addressed by the author and can be accepted for publications.

Reviewer #2: (No Response)

Reviewer #4: (No Response)

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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: No

Reviewer #2: Yes: Ahmed S Abouhashem

Reviewer #4: No