PONE-D-20-26541

Identification of Glioma-Related Potential Genes and Drugs: Based on GEO Database and Mining text

PLOS ONE

Dear Dr. Wang,

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,

Edwin Wang

Academic Editor

PLOS ONE

Additional editor comments:

1) Please clarify in the GO/KEGG analysis the p values were FDR-adjusted

2) Please clarify if statistical measures have been used in the drug-gene analysis

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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

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

Reviewer #1: No

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: No

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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: According to the policy of PLoS One, here I will only comment about the technical issues of the manuscript:

1. There are several glioma gene expression datasets in GEO database. Why did the authors consider only GSE31095, which is a relatively old, small-size microarray dataset in the analysis? Considering consensus DEGs in multiple gene expression datasets will prominently improve the confidence of the resulted gene list.

2. As for the drug analysis, the authors picked the drugs targeting hub genes (which were mostly known cancer driver genes) as the potential glioma-related drugs. The authors can implement gene expression-based drug analysis like Connectivity Map analysis to validate the predicted drugs.

3. The threshold of statistical significance was vague: P-value, adjusted P-value, or FDR, which one was used should be consistent.

4. Grammatical errors, awkward expressions or typos could be observed in nearly everyy paragraph of the manuscript. For example, the title should be “Computational Screening of Potential Glioma-Related Genes and Drugs Based on Analysis of GEO Dataset and Text Mining” rather than “Identification of Glioma-Related Potential Genes and Drugs: Based on GEO Database and Mining text”. Careful language editing by a native speaker is necessary before further consideration of the manuscript.

Reviewer #2: The authors identified some potential Glioma-related genes and available drugs based on analyzing GEO datasets and mining text. I hope the manuscript could be further strengthened by the following comments.

1. Please clearly state the major innovation of this work.

2. I want to know whether the researches for verifying your identification (the researches of Swoboda et al. and Shi et al.) are included in the GenCLIP3 platform for text mining.

3. I want to know whether this method can also be used for the analysis of other cancer.

4. You should revise your English writing carefully and eliminate small errors in the paper to make the paper easier to understand.

5. Could you give some discussions whether your method could be used to predict glioma-related potential non-coding RNAs as the future direction of this work (PMIDs: 29939227, 29045685, 30142158, and 27345524)?

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6. 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.

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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

[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.]

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PONE-D-20-26541R1

Computational Screening of Potential Glioma-Related Genes and Drugs Based on Analysis of GEO Dataset and Text Mining

PLOS ONE

Dear Dr. Wang,

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 Feb 18 2021 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.

Please include the following items when submitting your revised manuscript:

• A rebuttal 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 you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

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: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Edwin Wang

Academic Editor

PLOS ONE

[Note: HTML markup is below. Please do not edit.]

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: (No Response)

Reviewer #2: (No Response)

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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: Partly

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 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

**********

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: (No Response)

Reviewer #2: 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: The authors have addressed or explained most of my previous points except Major point 1. Without supporting evidence from another gene expression dataset, the technical quality requirement, which is emphasized by PLoS One journal, could not be met. On the other hand, this is not a hard task: The authors can simply find another glioma RNA-Seq dataset from GEO, intersect its differentially expressed genes with GenCLIP3 gene set, and perform GO and KEGG functional enrichment analysis. If there are some overlap of the enriched function terms between the new and the previous analyses, the result of this manuscript should be much more consolidated.

Besides, I would also like to point out that adjusted p-value and FDR are actually NOT the same thing. There are several statistical methods for p-value adjustment against multiple tests; and FDR, often following the Benjamini family of methods, is one category of adjusted p-value.

Reviewer #2: Authors should carefully check the information of references. For example, the author of [64] should be Chen X, Wang L, Qu J, Guan N-N, Li J-Q and its volume, issue and page number should be 34(24): 4256-4265; the year, volume, issue and page number of [66] should be 2017 18(4):558-576; the author of [67] should be Chen X, Yin J, Qu J, Huang L and its page number should be e1006418.

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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

[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.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Computational Screening of Potential Glioma-Related Genes and Drugs Based on Analysis of GEO Dataset and Text Mining

PONE-D-20-26541R2

Dear Dr. Wang,

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,

Edwin Wang

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: