PONE-D-22-07850Integrative Weighted Molecular Network Construction from Transcriptomics and Genome Wide Association Data Identified Shared Genetic Biomarkers for COPD and Lung CancerPLOS ONE

Dear Dr. Banaganapalli,

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Grant Number: G-593-140-1441

Full Name of Funder: Deanship of Scientific Research (DSR), King Abdulaziz University

URL: https://dsr.kau.edu.sa/

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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: Yes

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: 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

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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 original article by Banaganapalli and colleagues sought to identify significant changes in COPD and lung cancer. The authors collected transcriptomics and protein-protein interaction networks, and then discovered some differentially expressed genes, that are analyzed by some bioinformatics approaches and are available in silico datasets. They further predicted these clinicopathological events and patient outcomes through the features they selected. Other comments are listed as follows

• There are different stages of COPD to determine the severity of disease status, is there any difference among their gene expression?

• Some figures have poor pixels and the font is too small.

• They did not describe the statistical algorithm and p-value of each website and panel.

• The number of DEGs in manuscript and figure 1B are different.

• Some of the web links they provide cannot be entered

• There is no title of Table 4. It is also better to use scoring system to quantify and present the IHC results of these genes.

Reviewer #2: In the present study, the authors aim to identify potential biomarkers for COPD diagnosis and prognosis by analyzing the dysregulated gene expression patterns from blood and lung tissues. They identified many common DEGs from blood and lung tissue datasets and focused on 12 hub genes with DC score of >17. They further performed PPI analysis, GO analysis and GWAS to reveal the significance of 12 hub genes in COPD and lung cancer. They provided massive and valuable information about COPD and lung cancer.

Minor Points:

1. There are many references without formal styles such as Ref #10, #12, #13, #20, #28 #31, #39 and The Ref#16 is wrongly embedded. The authors should correct them.

2. The refractive asthma should be corrected as refractory asthma.

3. There are many inconsistencies among figures, legends and contexts such as Figure 1 & 3 and table

4. 12 significant genes should be with more than 17 of DC in the legends of Table 1 and Figure 2.

5. Go-annotations should be corrected as GO-annotations in Figure 3.

6. The items in table 1 should be re-modify to a professional one and the style in the column of Term Description should be consistent.

7. The image and staining intensity of MECOM from HPA database compared to Figure S3 were wrongly embedded and the authors should correct them.

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Reviewer #1: No

Reviewer #2: Yes: Magesh Ramasamy

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Integrative Weighted Molecular Network Construction from Transcriptomics and Genome Wide Association Data Identified Shared Genetic Biomarkers for COPD and Lung Cancer

PONE-D-22-07850R1

Dear Dr. Banaganapalli,

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,

Narasimha Reddy Parine, Ph.D

Academic Editor

PLOS ONE

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

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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 #3: Yes

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

Reviewer #1: Yes

Reviewer #3: 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: Yes

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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: 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: (No Response)

Reviewer #3: In this study, the authors analyzed the gene expression differences between the blood and lung tissues of COPD patients to identify diagnostic and prognostic biomarkers. They have performed multiple computational biology analysis methods (differential gene expression analysis, gene networking, hub gene identification, GO annotations, and druggability analysis) to discover the genetic biomarkers. They have also queried the candidate hub genes in GWAS and in cancer expression databases to understand their contribution to lung cancer. The manuscript is well written. The number of figures and tables is sufficient. I am convinced that the new information identified in COPD may lead to developing future treatment strategies. Therefore, I sincerely recommend this article for publication in your journal.

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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 #3: No

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