-->PONE-D-25-55299-->-->Comparative Gene Co-Expression Network Analysis of Antiviral and Immune Responses to Dengue-2 and Zika Virus Infection in Human Neural Progenitor Cells ((hNPCs)-->-->PLOS One

Dear Dr. Siam,

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 by both reviewers #1 and #2.

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Academic Editor

PLOS One

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2. We noticed you have some minor occurrence of overlapping text with the following previous publication(s), which needs to be addressed:

Gene coexpression network during ontogeny in the yellow fever mosquito, Aedes aegypti - https://doi.org/10.1186/s12864-023-09403-4

Transcriptome analysis of Aedes aegypti Aag2 cells in response to dengue virus-2 infection - https://doi.org/10.1186/s13071-020-04294-w

(Among others)

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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: 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: This manuscript describes the in silico analysis of RNA-Seq data obtained from dengue virus and Zika virus infections in human progenitor neural cells (hNPCs). Using Weighted Comparative Gene Co-expression Network Analysis (WGCNA), the authors identified clear differences in the gene expression patterns of dengue virus versus Zika virus-infected hNPCs. While several of the activated pathways are common to both types of infections, as expected, Dengue virus activated genes module showed more of an antiviral innate immunity activation signature, while the Zika virus module showed pathways more related to nucleic acid metabolism and cellular biological processes. The manuscript is well-written (albeit figure legends are misplaced along the text; they shall be all toghter at the end after the reference list), and the results are of interest since they highlights differences in the virus-cell interactions between these two viruses of public health importance.

Comments:

1. Material and Methods section. The authors should explain better the criteria used to select the RNA-Seq samples to be downloaded and analyzed from the NCBI SRI files. It will help the reader if the authors provide details of the infection conditions used to generate the RNA-Seq data chosen for their analysis.

2. Discussion section. Authors may discuss how the results may explain the neurotropism shown by the Zika virus but not by the dengue virus in infected patients.

Reviewer #2: In the manuscript by Owaresat et al., the author perform in in-depth analysis of RNA-seq data from human cells infected with DENV or ZIKV. There analysis is described well in the methods, and their description of the results is easy to follow. The discussion of the data is interesting to the reader.

My only minor comment is regarding the data sets. Are these published anywhere else, or is this manuscript the first analysis of these data? I could not find any reference to the data except the link to the SRA reads. The authors need to clarify.

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Reviewer #1: No

Reviewer #2: No

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Comparative Gene Co-Expression Network Analysis of Antiviral and Immune Responses to Dengue-2 and Zika Virus Infection in Human Neural Progenitor Cells ((hNPCs)

PONE-D-25-55299R1

Dear Dr. Siam,

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,

Qiang Shawn Chen, 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

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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

**********

-->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: None.XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX.

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: Yes: Alan Goodman

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