Dear Dr. Geng,

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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We look forward to receiving your revised manuscript.

Kind regards,

Fazul Nabi

Academic Editor

PLOS ONE

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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?

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: N/A

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3. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #1: Yes

Reviewer #2: No

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4. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: No

Reviewer #2: Yes

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Reviewer #1: Reviewer comments regarding the manuscript titled “Potential mechanisms and effects of AFB1-induced asthma: a comprehensive analysis based on network toxicology and molecular docking”

Title: Seems appropriate to the contents of the manuscript.

Abstract: The abstract is well written with few minor grammatical errors which needs to be addressed before final submission.

Introduction: The manuscript is not having any line numbers so its hard to communicate with the author but there are few grammatical errors such as words with no spacing and wrong grammar in this section. Please address the concern before final submission.

Materials and Methods: This section is clearly written but minor grammar errors needs to be addressed before final submission please.

Results: Please check for grammar and remove English language errors. Please also follow superscript or under script in formula of AFB1. Lines are not justified throughout the manuscript but specifically in this section.

Discussion: This section is well written and explained but please check for grammatical errors.

Conclusion: well written and explained.

No acknowledgment or funding or conflict of interest statement found in the manuscript?

References: Please format references according to the journal requirements.

Figures: would you be able to please improve the quality of figures shown in the manuscript and improve its visibility?

Reviewer #2: General assessment: The manuscript entitled “Potential mechanisms and effects of AFB1-induced asthma: a comprehensive analysis based on network toxicology and molecular docking” explores a novel and under-investigated topic, the potential molecular mechanisms linking Aflatoxin B1 exposure with asthma pathogenesis, using an integrative in silico workflow combining network toxicology, enrichment analysis, and molecular docking. The study is timely, conceptually interesting, and provides biologically plausible hypotheses regarding GPCR signaling, arachidonic acid metabolism, and oxidative stress in AFB1-related airway dysfunction. The manuscript is generally well organized and clearly written. However, several methodological and reporting issues need to be addressed to ensure reproducibility and alignment with PLOS ONE transparency standards.

Major comments:

1. Database and software versioning: please provide detailed versions and access dates for all databases and tools used: ChEMBL, STITCH, SwissTargetPrediction, GeneCards, OMIM, TTD, STRING, ProTox, ADMETlab, and the specific software (R and packages, Cytoscape, AutoDock or equivalent).

2. GO/KEGG enrichment statistics: clearly state the multiple-testing correction method (e.g., Benjamini–Hochberg FDR), the p.adjust threshold used for significance, and attach full result tables (GO/KEGG term ID, description, geneRatio, p.adjust, and gene list) as supplementary CSV files.

3. STRING and PPI network parameters: Specify the confidence score cutoff, the evidence channels included (e.g., experiment, database, text mining), and the organism setting used. Please include the full STRING export (.tsv) as a supplementary file.

4. Hub gene identification: Indicate the algorithm and metric used in CytoHubba (e.g., Degree, MCC, Betweenness) and provide a table listing the top 10 genes with their centrality scores.

5. Molecular docking reproducibility: provide complete details on receptor and ligand preparation, grid box coordinates and size, exhaustiveness, number of poses, and validation steps (e.g., re-docking RMSD < 2 Å). Include a summary table with docking energy values (mean ± SD, kcal/mol), key interacting residues, and hydrogen/hydrophobic bonds. Add positive and negative controls if available.

6. Data and code availability: deposit all raw data, scripts (e.g., Toxicity.venn.R), intermediate files (TXT, TSV, CSV), and figure sources in a public repository such as Zenodo or OSF and update the Data Availability Statement with a DOI link.

7. Discussion and limitations: the Discussion should go beyond result description. Please deepen biological interpretation, include literature comparisons, and explicitly acknowledge the in silico limitations and potential database biases. Rephrase causal statements into hypothesis-generating language (e.g., “may contribute,” “suggests”).

Minor comments

1. Define all abbreviations at first mention (e.g., GPCR, ADMET).

2. Revise the writing for conciseness and grammar consistency; unify past tense throughout Methods and Results.

3. Improve figure legends to include sample sizes, p.adjust scale, and database sources/versions.

4. Include a table summarizing all databases and software (name, version, access date, URL).

5. Cite the official reference articles for the databases and tools (SwissTargetPrediction, STRING, ProTox-II, ADMETlab).

6. Ensure that reference formatting follows PLOS ONE style (numbered citations in square brackets).

The manuscript presents a coherent and potentially impactful in silico investigation. Once the methodological transparency and docking reproducibility issues are resolved, the study would meet PLOS ONE publication standards.

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what does this mean? ). If published, this will include your full peer review and any attached files.

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Reviewer #1: Yes:  Syed Zahid Ali Shah

Reviewer #2: No

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[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.]

To ensure your figures meet our technical requirements, please review our figure guidelines: https://journals.plos.org/plosone/s/figures

You may also use PLOS’s free figure tool, NAAS, to help you prepare publication quality figures: https://journals.plos.org/plosone/s/figures#loc-tools-for-figure-preparation.

NAAS will assess whether your figures meet our technical requirements by comparing each figure against our figure specifications.

Dear Dr. Geng,

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.

Please submit your revised manuscript by Jan 30 2026 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.

• A 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 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,

Fazul Nabi

Academic Editor

PLOS One

Journal Requirements:

1. If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise.

2. 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

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

Reviewer #2: Yes

**********

Reviewer #1: (No Response)

Reviewer #2: Reviewer Comments – Second Round

I would like to thank the authors for the extensive work carried out in preparing this revised version. The manuscript shows clear improvements in clarity, structure, and methodological detail. I appreciate the thoughtful responses to the previous comments and the effort invested in strengthening the study. Only a few minor points remain that, once clarified, will further enhance the transparency and interpretability of the manuscript.

1. Molecular docking methodology

The additional information provided in the supplementary material is very helpful. To improve reproducibility directly from the main text, it would be beneficial to briefly include: the exhaustiveness parameter used in AutoDock Vina, the number of poses generated, and whether any positive or negative controls were considered (or a short explanation if they were not used). A concise addition to the Methods would be sufficient.

2. Interpretation of in silico findings

The authors have made an effort to adjust several statements in the Discussion, which is appreciated. For clarity, I kindly suggest slightly softening a few remaining phrases that may appear to imply causality based solely on in silico predictions. Emphasizing the exploratory and hypothesis-generating nature of network toxicology and docking will help align the interpretation with the strengths of these methods.

3. Enrichment analysis presentation

The enrichment analysis is now clearer with the inclusion of FDR correction. If possible, adding metrics such as geneRatio or a similar indicator in the supplementary tables would give readers additional context regarding the weight of each enriched category.

Overall assessment

The manuscript is very close to final form. The remaining points are minor and should be straightforward to address. I appreciate the authors’ careful revisions and believe the study will be strengthened with these small clarifications.

Recommendation: Minor Revision

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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: Yes:  Prof. Dr. Syed Zahid Ali Shah

Reviewer #2: No

**********

[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.]

To ensure your figures meet our technical requirements, please review our figure guidelines: https://journals.plos.org/plosone/s/figures

You may also use PLOS’s free figure tool, NAAS, to help you prepare publication quality figures: https://journals.plos.org/plosone/s/figures#loc-tools-for-figure-preparation.

NAAS will assess whether your figures meet our technical requirements by comparing each figure against our figure specifications.

Potential mechanisms and effects of AFB1-induced asthma: a comprehensive analysis based on network toxicology and molecular docking

PONE-D-25-52273R2

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,

Fazul Nabi

Academic Editor

PLOS One