Selected by bioinformatics and molecular docking analysis, Dhea and 2–14,15-Eg are effective against cholangiocarcinoma

Lei Qin; Jun Kuai; Fang Yang; Lu Yang; Peisheng Sun; Lanfang Zhang; Guangpeng Li

doi:10.1371/journal.pone.0260180

Peer Review History

Original SubmissionAugust 11, 2021
14 Oct 2021 Decision Letter - Nafees Ahemad, Editor PONE-D-21-25842Selected by bioinformatics and molecular docking analysis, Dhea and 2-14,15-Eg are effective against cholangiocarcinomaPLOS ONE Dear Dr. Li, 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 Nov 28 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. 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Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: No 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: Yes ****** 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: The authors in their manuscript titled "Selected by bioinformatics and molecular docking analysis, Dhea and 2-14,15-Eg are effective against cholangiocarcinoma" have attempted to to study the therapeutic effect of Dhea and 2-14,15-Eg on cholangiocarcinoma. Though the intention of the study is good, the results presented based on preliminary analysis does not merit publication in a journal of repute like PLOS ONE. Reviewer #2: This is an interesting study with extensive analysis in identifying the drug candidates for cholangiocarcinoma. However, there are several issues that need to be clarified. 1. In the introduction part, the authors may provide several examples of previous studies that utilize similar approaches. 2. Several abbreviations were not defined, such as PPI, FGFR and others. Please double check. 3. All tools and databases such as MCODE, Metascape, ZINC15 database, KEGG database, etc. should be cited and provided in the reference list. 4. Materials and methods - GO and KEGG pathway enrichment analysis: what are the statistical test that were used by DAVID to identify significant GOs and pathways. 5. The figures were not cited in read order in the manuscript text. For example, Figure 4A was mentioned before Figure 1. Figure 1C were cited after figure 2a and figure 2b. The authors should reorganize on the in-text citations of the figures. 6. Several figures were not mentioned in the text. Please double check on this. 7. I think Figure 1C should be located at Figure 2, under GO and pathway enrichment analysis. 8. Please double check the Figure label of Figure 2. 9. What are the color nodes in the Figure 3 represent? Please explain this in Figure caption. 10. Each figure should have a figure title. The authors only provide the figure legends. You may refer this issue at this link https://journals.plos.org/plosone/s/figures#loc-how-to-submit-figures-and-captions. 11. 21 hub genes were mentioned in the text, but only 20 hub genes were listed in the Table 1. 12. The authors may separate the hub genes and module screening into two subsections by either adding another subsection or rename the title of this subsection (Module Screening from the PPI Network). You may also provide the total number of nodes and edges for the PPI network. 13. How many modules were generated by MCODE? 14. Among these genes, the node degree of ALB was the highest, followed by MYC with 50. This sentence is hanging. 50 of what? 15. The functional annotation and enrichment of modules genes were shown in Table. Which table? 16. Select the crystal structure of MYC as the receptor. You should rephrase this sentence. 17. It is better to provide the compounds name in the table 2, table 3 and supplementary table 3. 18. Majority of the figures and the figure labels are not clear. 19. In the discussion part, the authors may discuss the importance of hub genes in human diseases. 20. What is the purpose of performing module selection? Is MYC detected in the modules? Can you discuss this result in the discussion? ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). 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Revision 1
30 Oct 2021 Author Response Dear Editors: Thank you for the valuable comments of our manuscript entitled “Selected by bioinformatics and molecular docking analysis, Dhea and 2-14,15-Eg are effective against cholangiocarcinoma”. We have studied the comments carefully and have made corrections in the manuscript which we hope to meet with approval. The main corrections in the paper and the responses to editor’s comments are as following. Review Comments to the Author Reviewer #1: The authors in their manuscript titled "Selected by bioinformatics and molecular docking analysis, Dhea and 2-14,15-Eg are effective against cholangiocarcinoma" have attempted to to study the therapeutic effect of Dhea and 2-14,15-Eg on cholangiocarcinoma. Though the intention of the study is good, the results presented based on preliminary analysis does not merit publication in a journal of repute like PLOS ONE. Response： Thanks for your comments, but I don't agree with you someway. Natural molecules have contributed significantly to not only molecular biological research but also potential drug development. A number of relevant studies have been published in reputable journals. Besides, we carried out this research with great care and precision and MTT assay, colony-forming assay, the scratch assay and Western blotting were performed to verify our findings. I hope you could reconsider it again, and your opinion is very important to us. Thank you very much. [1] Li, W., et al., Ten-gene signature reveals the significance of clinical prognosis and immuno-correlation of osteosarcoma and study on novel skeleton inhibitors regarding MMP9. Cancer Cell Int, 2021. 21(1): p. 377. [2] Zhong, S., et al., Selected by gene co-expression network and molecular docking analyses, ENMD-2076 is highly effective in glioblastoma-bearing rats. Aging (Albany NY), 2019. 11(21): p. 9738-9766. Reviewer #2: This is an interesting study with extensive analysis in identifying the drug candidates for cholangiocarcinoma. However, there are several issues that need to be clarified. 1. In the introduction part, the authors may provide several examples of previous studies that utilize similar approaches. 2. Several abbreviations were not defined, such as PPI, FGFR and others. Please double check. 3. All tools and databases such as MCODE, Metascape, ZINC15 database, KEGG database, etc. should be cited and provided in the reference list. 4. Materials and methods - GO and KEGG pathway enrichment analysis: what are the statistical test that were used by DAVID to identify significant GOs and pathways. 5. The figures were not cited in read order in the manuscript text. For example, Figure 4A was mentioned before Figure 1. Figure 1C were cited after figure 2a and figure 2b. The authors should reorganize on the in-text citations of the figures. 6. Several figures were not mentioned in the text. Please double check on this. 7. I think Figure 1C should be located at Figure 2, under GO and pathway enrichment analysis. 8. Please double check the Figure label of Figure 2. 9. What are the color nodes in the Figure 3 represent? Please explain this in Figure caption. 10. Each figure should have a figure title. The authors only provide the figure legends. You may refer this issue at this link https://journals.plos.org/plosone/s/figures#loc-how-to-submit-figures-and-captions. 11. 21 hub genes were mentioned in the text, but only 20 hub genes were listed in the Table 1. 12. The authors may separate the hub genes and module screening into two subsections by either adding another subsection or rename the title of this subsection (Module Screening from the PPI Network). You may also provide the total number of nodes and edges for the PPI network. 13. How many modules were generated by MCODE? 14. Among these genes, the node degree of ALB was the highest, followed by MYC with 50. This sentence is hanging. 50 of what? 15. The functional annotation and enrichment of modules genes were shown in Table. Which table? 16. Select the crystal structure of MYC as the receptor. You should rephrase this sentence. 17. It is better to provide the compounds name in the table 2, table 3 and supplementary table 3. 18. Majority of the figures and the figure labels are not clear. 19. In the discussion part, the authors may discuss the importance of hub genes in human diseases. 20. What is the purpose of performing module selection? Is MYC detected in the modules? Can you discuss this result in the discussion? Response：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. 1.The similar approaches had been provided in the introduction part. 2.Thanks for your comment. The all abbreviations were provided. 3.All tools and databases had been cited and provided in the reference list. 4. In DAVID, Fisher's Exact test is adopted to measure the gene-enrichment in annotation term, and P < 0.05 and counts > 2 were set as the threshold values. Significant GOs and pathways is filtered by this threshold. 5.The order of figures had been revised. 6.Thanks for your comment. We had checked it and mentioned all figures in this manuscript. 7.We had revised it. 8.The Figure label of Figure 2 had been revised. 9.The color nodes of Figure 3 had been explained in figure captions. The degrees of nodes were labeled in different colors, the red color means bigger degrees. 10.The figure titles had been provided. 11.We had checked it and corrected the number. 12.We had revised this part as your comment, and the total number of nodes and edges for PPI network also been provided. 13.There are 14 modules were generated by MCODE. 14. We had revised this sentence. 15. The table was provided. 16. We had revised this sentence. 17.The compounds name in the table 2, table 3 and supplementary table 3. 18.The figures and the figure labels are revised, and 300dpi figures were provided. 19.The importance of hub genes in human diseases were discussed in discussion section. 20. MCODE is a technique for detecting densely connected regions in huge protein-protein interaction networks that could be molecular complexes. Predicting molecular complexes is crucial because it provides another level of functional annotation. Since sub-units of a molecular complex generally function towards the same biological process, prediction of an unknown protein as part of a complex also allows increased confidence in the annotation of that protein. Performing module selection and the result were discussed. MYC is also detected in the modules. Dear Editors, Thank you for your work dealing with this manuscript, thank you very much. If there is any problem, please don’t hesitate to contact us. I will reply you as soon as possible. Best wishes to you. May its blessings lead into a wonderful year for you and all whom you love. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0260180.r002
4 Nov 2021 Decision Letter - Nafees Ahemad, Editor Selected by bioinformatics and molecular docking analysis, Dhea and 2-14,15-Eg are effective against cholangiocarcinoma PONE-D-21-25842R1 Dear Dr. Li, 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 for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, 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, Nafees Ahemad Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0260180.r003
Formally Accepted
21 Jan 2022 Acceptance Letter - Nafees Ahemad, Editor PONE-D-21-25842R1 Selected by bioinformatics and molecular docking analysis, Dhea and 2-14,15-Eg are effective against cholangiocarcinoma Dear Dr. Li: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. 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 plosone@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. Nafees Ahemad Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0260180.r004

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