TabDEG: Classifying differentially expressed genes from RNA-seq data based on feature extraction and deep learning framework

Sifan Feng; Zhenyou Wang; Yinghua Jin; Shengbin Xu

doi:10.1371/journal.pone.0305857

Peer Review History

Original SubmissionSeptember 21, 2023
2 Jan 2024 Decision Letter - Divijendra Natha Reddy Sirigiri, Editor PONE-D-23-30756TabDEG: Classifying differentially expressed genes from RNA-seq data based on feature extraction and deep learning frameworkPLOS ONE Dear Dr. JIN, 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 16 2024 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: 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, Divijendra Natha Reddy Sirigiri Academic Editor PLOS ONE Journal Requirements: When submitting your revision, we need you to address these additional requirements. 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf 2. Note from Emily Chenette, Editor in Chief of PLOS ONE, and Iain Hrynaszkiewicz, Director of Open Research Solutions at PLOS: Did you know that depositing data in a repository is associated with up to a 25% citation advantage (https://doi.org/10.1371/journal.pone.0230416)? If you’ve not already done so, consider depositing your raw data in a repository to ensure your work is read, appreciated and cited by the largest possible audience. You’ll also earn an Accessible Data icon on your published paper if you deposit your data in any participating repository (https://plos.org/open-science/open-data/#accessible-data). 3. Please note that PLOS ONE has specific guidelines on code sharing for submissions in which author-generated code underpins the findings in the manuscript. In these cases, all author-generated code must be made available without restrictions upon publication of the work. Please review our guidelines at https://journals.plos.org/plosone/s/materials-and-software-sharing#loc-sharing-code and ensure that your code is shared in a way that follows best practice and facilitates reproducibility and reuse. 4. Please update your submission to use the PLOS LaTeX template. The template and more information on our requirements for LaTeX submissions can be found at http://journals.plos.org/plosone/s/latex. 5. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information. 6. We are unable to open your Supporting Information file [figures.rar]. Please kindly revise as necessary and re-upload. [Note: HTML markup is below. Please do not edit.] 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 ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 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 ****** 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 ****** 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: It's my honor to receive the manuscript entitled 'TabDEG: Classifying differentially expressed genes from RNA-seq data based on feature extraction and deep learning framework'. Feng et al offered a TabDEG model which combines DA and TabNet, aiming to solve multiple classification problems, such as classifying DEGs and predicting UR/DR direction.However, it is highly recommended that you address the issues listed before submitting. Please see comments below: 1. The authors should mention in detail how they selected the 10 different tumor types characteristic (Age, gender, stage, TNM, et al) for the experiment and discuss the potential bias of the results. 2. The author should justify using logfc > 1 as a threshold for DEGs identification. 3.Necessary references should be added, such as the section on "Path enrich analysis of predicted UR and DR genes". 4.English needs to be improved by English editing service or a native English speaker. Reviewer #2: The work is interesting. This paper designs framework for predicting DEGs. Although the promising results have been achieved, several major concerns in the current manuscript show that it appears that publication in any form would be premature at this time. 1. The relationship between the data downloaded from UCSX Xena Data Browser (https : //xenabrowser.net/datapages/) and the data of TCGA should be listed. 2.” Import the ”tidyverse” package and then start pre-processing the gene expression data. RNA transcripts with an expression level greater than 1 are screened out and a total of 17983 RNA transcripts are screened. The screen-obtained datasets are divided into T and N, which are used as control conditions in next step.” Here, how to divide the two datasets ”T” and “N”? 3. The readability of writing is poor, which makes the manuscript is difficult to be understood. 4. Tables 3 and 4 can be combined and shown graphically. 5. Including the benchmarking algorithms, what is the input of the algorithms? What kind of feature extraction method is used? 6. It was suggested that authors should share the code and data in this work. ****** 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. 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: Qinglu Wang 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. Attachments Attachment Submitted filename: review.docx https://doi.org/10.1371/journal.pone.0305857.r001
Revision 1
20 Feb 2024 Author Response Dear Editors and Reviewers: Thank you for your letter and for the reviewers’ comments concerning our manuscript entitled “TabDEG: Classifying differentially expressed genes from RNA-seq data based on feature extraction and deep learning framework” (PONE-D-23-30756). Those comments are all valuable and very helpful for revising and improving our paper, as well as the important guiding significance to our researches. We have studied comments carefully and have made correction which we hope meet with approval. The maincorrections in the paper and the responds to the reviewer's comments are as flowing: Responds to the reviewer's comments: Reviewer#1: 1.Response to comment: The authors should mention in detail how they selected the 10 different tumor types characteristic (Age, gender, stage, TNM, et al) for the experiment and discuss the potential bias of the results. Response: The TCGA dataset selected in this paper comes from a variety of samples from patients with different regions, races and clinical characteristics, and thus contains different genomic information, which helps to reduce group bias and improve the representativeness of the results. Meanwhile, different tumor types may have different characteristics, development patterns, and treatments, so by using datasets of multiple tumor types, the over-reliance on specific tumor types can be reduced, and the generalization ability of the algorithm can be improved, making it more robust in dealing with unknown or novel tumor types. Relevant revisions we have marked in yellow color in the "Data Collection and Preprocessing" section of the revised manuscript. 2.Response to comment:The author should justify using logfc > 1 as a threshold for DEGs identification. Responsc: LogFC > 1 indicates at least a 2-fold change in the expression level of a gene between two conditions, and such a change is considered to be relatively large to provide a higher significance difference and thus more likely to reflect biological importance. In many related studies, logFC > 1 is considered a reasonable threshold for screening out DEGs of functional and biological importance. Relevant revisions we have marked in yellow color in the "Data Collection and Preprocessing" section of the revised manuscript. 3.Response to comment:Necessary references should be added, such as the section on "Path enrich analysis of predicted UR and DR genes". Responsc: We sincerely appreciate the valuable comments. We have checked the literature carefully and added more references into the section on "Path enrich analysis of predicted UR and DR genes" part in the revised manuscript. 4.Response to comment:English needs to be improved by English editing service or a native English speaker. Responsc: Thanks for your suggestion. We have tried our best to polish the language in the revised manuscript. Reviewer#2: 1.Response to comment: The relationship between the data downloaded from UCSX Xena Data Browser (https : //xenabrowser.net/datapages/) and the data of TCGA should be listed. Response: The UCSX Xena Data Browser serves as a data browser that provides access to and analyzes TCGA data. Relevant revisions we have marked in red color in the "Data Collection and Preprocessing" section of the revised manuscript. 2.Response to comment: ” Import the ”tidyverse” package and then start pre-processing the gene expression data. RNA transcripts with an expression level greater than 1 are screened out and a total of 17983 RNA transcripts are screened. The screen-obtained datasets are divided into T and N, which are used as control conditions in next step.” Here, how to divide the two datasets ”T” and “N”? Response: The tumor and normal groups will be labeled "01A" and "11A" respectively in the column names of the TCGA dataset, and based on this the dataset will be categorized into "T" and "N" groups. Relevant revisions we have marked in red color in the "Data Collection and Preprocessing" section of the revised manuscript. 3.Response to comment: The readability of writing is poor, which makes the manuscript is difficult to be understood. Response: Thanks for your suggestion. We have tried our best to polish the language in the revised manuscript. 4.Response to comment: Tables 3 and 4 can be combined and shown graphically. Response: We have completed the relevant revisions in the Table 3 of the revised manuscript. 5.Response to comment: Including the benchmarking algorithms, what is the input of the algorithms? What kind of feature extraction method is used? Response: The input to the algorithm is RNA-seq counts data, and the feature extraction uses a combination of pca, k-means and umap for dimensionality reduction extraction. 6.Response to comment: It was suggested that authors should share the code and data in this work. Response: We will share the code and data from this work in the Supporting Information. Special thanks to you for your good comments. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0305857.r002
1 Apr 2024 Decision Letter - Divijendra Natha Reddy Sirigiri, Editor PONE-D-23-30756R1TabDEG: Classifying differentially expressed genes from RNA-seq data based on feature extraction and deep learning frameworkPLOS ONE Dear Dr. JIN, 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 May 16 2024 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: 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, Divijendra Natha Reddy Sirigiri Academic Editor PLOS ONE Journal Requirements: 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 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 #2: (No Response) ******** 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 #2: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? 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 #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 #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 #2: Authors should share the code and data in this work，it can be posted on GitHub instead of screenshots in supplementary materials ****** 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 #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. https://doi.org/10.1371/journal.pone.0305857.r003
Revision 2
10 May 2024 Author Response Dear Editors and Reviewers: Thank you for your letter and for the reviewers’ comments concerning our manuscript entitled “TabDEG: Classifying differentially expressed genes from RNA-seq data based on feature extraction and deep learning framework” (PONE-D-23-30756R1). Those comments are all valuable and very helpful for revising and improving our paper, as well as the important guiding significance to our researches. We have studied comments carefully and have made correction which we hope meet with approval. The maincorrections in the paper and the responds to the reviewer's comments are as flowing: Responds to the reviewer's comments: Reviewer#2: Authors should share the code and data in this work，it can be posted on GitHub instead of screenshots in supplementary materials Response: Thanks for the correction, we have posted the code and data in this work on GitHub, which can be viewed at the link: https://github.com/xueyupi/my_tabdeg Special thanks to you for your good comments. Attachments Attachment Submitted filename: Response to Reviewers2.docx https://doi.org/10.1371/journal.pone.0305857.r004
6 Jun 2024 Decision Letter - Divijendra Natha Reddy Sirigiri, Editor TabDEG: Classifying differentially expressed genes from RNA-seq data based on feature extraction and deep learning framework PONE-D-23-30756R2 Dear Dr. JIN, 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. An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Divijendra Natha Reddy Sirigiri Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0305857.r005
Formally Accepted
11 Jul 2024 Acceptance Letter - Divijendra Natha Reddy Sirigiri, Editor PONE-D-23-30756R2 PLOS ONE Dear Dr. Jin, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks to review your paper and let you know the next and final steps. Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. If we can help with anything else, please email us at customercare@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Divijendra Natha Reddy Sirigiri Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0305857.r006

Open letter on the publication of peer review reports

PLOS recognizes the benefits of transparency in the peer review process. Therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. Reviewers remain anonymous, unless they choose to reveal their names.

We encourage other journals to join us in this initiative. We hope that our action inspires the community, including researchers, research funders, and research institutions, to recognize the benefits of published peer review reports for all parts of the research system.

Learn more at ASAPbio .