PONE-D-23-41835Genetic Insights into the Connection Between Pulmonary TB and Non-Communicable Diseases: An Integrated Analysis of Shared Genes and Potential Treatment TargetsPLOS ONE

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Academic Editor

PLOS ONE

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Reviewers' comments:

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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: Partly

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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: No

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: I wanted to comment upon the language of the paper, I can fully understand it is difficult for a non-native speaker to be fluent in English, but I expect the authors to improve the language of the manuscript thoroughly as the grammatical errors dilute the actual potential of the manuscript.

Reviewer #2: Authors have put in a commendable effort using bioinformatics in addressing one of the challenging questions in treatment of patients with comorbidities. In this article authors have investigated the genetic association between PTB and 7 NCDs. They show that genes such as TNF, IL10, NLRP3, IL18, IFNG, HMGB1, CXCL8, IL17A, and NFKB1 discovered were shared between TB and the NCDs, and five hub genes (NFKB1, TNF, CXCL8, NLRP3, and IL10) were found to be common among them. Moreover, they also suggested few drug candidates for the treatment. Although, further investigation is suggested for better treatment outcomes.

The manuscript is very well written.

However, I have one major concern:

Authors have shown NFKB1 as a potential target. Given the pleiotropic role of NFKB1, approach to target NFKB1 rather becomes interesting and the question of specificity immediately arises. It is vital to consider the underlying mechanisms of disease progression to obtain a required beneficial outcome while targeting NFKB1 in patients with comorbidities. Consider following situations involved in comorbidities:

a. In autoimmune diseases like RA immune system needs to be suppressed to alleviate the disease while in PTB need of effective immune system is essential.

b. In cancer, while rouge cells are required to be controlled, immune system needs bolstering.

Also, a more nuanced approach is advised such as targeting of subsets of NF-κB activities which, hopefully, will target pathogenic processes while leaving physiological processes largely intact.

Could the authors discuss the complication of targeting NFKB1, while it is one of the major hub genes as per their study is concerned.

Minor correction

Line no. 378- On the other hand, In tissue-specific PPI, the NFKB1 gene interacts with. Small case, ‘in’.

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Reviewer #1: Yes: SAKSHI SINGH

Reviewer #2: No

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Attachments

Attachment

Submitted filename: Plos one Manuscript_3_5_2024.docx

Genetic Insights into the Connection Between Pulmonary TB and Non-Communicable Diseases: An Integrated Analysis of Shared Genes and Potential Treatment Targets

PONE-D-23-41835R1

Dear Dr. Rahman,

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,

Jinhui Liu

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

I think this manuscript was well organized and it could be accepted.

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

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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

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

Reviewer #1: Yes

Reviewer #2: Yes

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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

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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 #2: Yes

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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 #2: (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: No

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