Comparative analysis of web-based programs for single amino acid substitutions in proteins

Arunabh Choudhury; Taj Mohammad; Farah Anjum; Alaa Shafie; Indrakant K. Singh; Bekhzod Abdullaev; Visweswara Rao Pasupuleti; Mohd Adnan; Dharmendra Kumar Yadav; Md. Imtaiyaz Hassan

doi:10.1371/journal.pone.0267084

Peer Review History

Original SubmissionNovember 11, 2021
26 Dec 2021 Decision Letter - Timir Tripathi, Editor PONE-D-21-35921Comparative analysis of web-based programs for single amino acid substitutions in proteinsPLOS ONE Dear Dr. Hassan, 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. ============================== The manuscript has been reviewed by three independent reviewers. They find merit in this manuscript but have highlighted several areas in which improvement and corrections are necessary. These areas include the organization of the text as well as technical details, and must be addressed for the manuscript to be considered for publication. Few language issues also need to be resolved by the authors. ============================== Please submit your revised manuscript by Feb 09 2022 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, Timir Tripathi, Ph.D. 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. We note that the grant information you provided in the ‘Funding Information’ and ‘Financial Disclosure’ sections do not match. When you resubmit, please ensure that you provide the correct grant numbers for the awards you received for your study in the ‘Funding Information’ section. 3. We note you have included a table to which you do not refer in the text of your manuscript. Please ensure that you refer to Table 3 in your text; if accepted, production will need this reference to link the reader to the Table. 4. 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. [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 Reviewer #3: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: N/A Reviewer #3: 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 Reviewer #3: 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: Yes Reviewer #2: Yes Reviewer #3: 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: 1. Introduction should be comprehensive. A discussion on the significance of these tools should be addressed. 2. The rationale to do such kind of review and analytical comparison must be described. 3. The calculations were performed on 15 different predictors. Are these tools based on the same prediction methods? Discuss this in the manuscript. 4. The authors used five different proteins in the study. What would be the results of calculations upon only one protein? 5. Were the average values estimated for all the parameters of each tool? 6. The explanation of the observed differences in the prediction power of each tool should be elaborated in light of their algorithms and resultant decision. 7. Authors double-check the manuscript for abbreviations used. 8. Language editing is required to improve the quality of the manuscript. The author should recheck this manuscript carefully and remove typos and grammatical errors. 9. All references should be thoroughly checked, and especially Author must confirm only relevant publications should be cited. Reviewer #2: This study compares various available bioinformatics tools for predicting the impact of mutations in human proteins on their structure and function. The scope of the study is wide, with over a dozen computational web-based tools to evaluate their prediction power. The current form of the manuscript, unfortunately, ignores the following points which need to be resolved during revision. · Despite interesting findings this paper lacks sound rationale and experimental support. The drawn conclusion should be focused and crisp. · What is the basis of selecting five different proteins in this study? Is there any evidence that SNPs under consideration in this study are associated with disease? Discuss the rationale for this. · Is there any clinical evidence showing that the destabilizing/deleterious nsSNPs are associated with protein dysfunction? · How was the comparison of different predictors batched? A little detail of each predictor must be addressed. · Method section may be shortened. · Discussion should be improved in light of the author's findings and previous literature. · The authors have not explained any relation between the prediction strategies of different predictors. This should be highlighted in the text. · It is necessary to write the reasons why different five proteins were used as the benchmark. · In conclusion, the authors write that “Out of the structure-based web tools, mCSM showed a higher number of mutations as destabilizing”. What does it mean? This statement should be elaborated. · The results section is redundant. Please revise, focusing on the specific outcomes and their importance. The strength of the author’s findings should be highlighted. · A uniform presentation is required. The author should proofread the manuscript before final submission. Reviewer #3: 1. Abstract: Can be concise and trim-down; repetitive meanings should be avoided. 2. The scientific problem is described well, however, there are a few language mistakes in the text. Therefore, language editing is required to improve the quality of the manuscript. Grammatical mistakes and typographical errors should be corrected. 3. Introduction: Some of the English terminology used is odd which needs to be updated during the revision. 4. Introduction, second paragraph, first sentence, needs citation. 5. The results section has some redundancy in many parts. Authors should update this, focusing on the specific outcomes and their significance. 6. It is not clear how the destabilizing parameters compared with the values estimated by different tools based on totally different approaches? 7. The terms deleterious/pathogenic/destabilizing should be described clearly, and their correlations with the prediction should be discussed. 8. Table 1, a column mentioning the reference for the corresponding tool, should be added. 9. Discussion should be focused. The author should adhere to the results obtained from experiments. 10. Conclusion should be crisp and focused. Outcome must be highlighted in the conclusion section. Conclusions should provide be more details and further highlight the work and its potential importance/application ****** 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: Tooba Naz Shamsi Reviewer #2: No Reviewer #3: Yes:** Dr. Ethayathulla Abdul samath [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.0267084.r001
Revision 1
27 Mar 2022 Author Response Journal: PLOS ONE Manuscript Title: Comparative analysis of web-based programs for single amino acid substitutions in proteins Manuscript ID: PONE-D-21-35921 Reviewer #1: 1. Introduction should be comprehensive. A discussion on the significance of these tools should be addressed. Response: Thank you for your valuable suggestion. Now we have discussed the introduction more compressively comprising the significance of each tool. 2. The rationale to do such kind of review and analytical comparison must be described. Response: The rationale of the study has been described now. 3. The calculations were performed on 15 different predictors. Are these tools based on the same prediction methods? Discuss this in the manuscript. Response: Different tools are not based on the same method. We have discussed this in the revised manuscript. 4. The authors used five different proteins in the study. What would be the results of calculations upon only one protein? Response: Five different proteins were used for high accuracy, involving the divorce datasets in the calculation. It minimizes the false prediction where only one protein can have less coherent outcomes. 5. Were the average values estimated for all the parameters of each tool? Response: No, the prediction was considered as yes or no for destabilizing mutation. 6. The explanation of the observed differences in the prediction power of each tool should be elaborated in light of their algorithms and resultant decision. Response: Thank you for your valuable suggestion. Now we have discussed the prediction power of all the tools and their algorithms more compressively. 7. Authors double-check the manuscript for abbreviations used. Response: The manuscript has been thoroughly checked for abbreviations and updated during this revision. Thanks! 8. Language editing is required to improve the quality of the manuscript. The author should recheck this manuscript carefully and remove typos and grammatical errors. Response: The manuscript has now been thoroughly checked and corrected for typos and language errors. 9. All references should be thoroughly checked, and especially Author must confirm only relevant publications should be cited. Response: The reference section has been updated now. Reviewer #2: This study compares various available bioinformatics tools for predicting the impact of mutations in human proteins on their structure and function. The scope of the study is wide, with over a dozen computational web-based tools to evaluate their prediction power. The current form of the manuscript, unfortunately, ignores the following points which need to be resolved during revision. • Despite interesting findings this paper lacks sound rationale and experimental support. The drawn conclusion should be focused and crisp. Response: Thank you for your valuable suggestion. Now we have highlighted the rationale and discussion part of the revised manuscript. • What is the basis of selecting five different proteins in this study? Is there any evidence that SNPs under consideration in this study are associated with disease? Discuss the rationale for this. Response: Multiple proteins were used to identify diseased mutations since studying only one protein can provide some false positives. To avoid any false prediction, multiple datasets were used, warranting more accuracy of the outcomes. Yes, there are several evidences SNPs under consideration are associated with disease progression. The text has been updated in the revised manuscript. • Is there any clinical evidence showing that the destabilizing/deleterious nsSNPs are associated with protein dysfunction? Response: There are several clinical findings that the destabilizing/deleterious nsSNPs of the selected proteins are associated with protein dysfunction resulting in disease progression. We have updated the discussion part of the revised manuscript. • How was the comparison of different predictors batched? A little detail of each predictor must be addressed. Response: The prediction was considered as an independent decision of each tool. Now we have described each predictor during this revision. • Method section may be shortened. Response: The method section has already been written briefly. Shortening the method section may cause intricacy for the readers. • Discussion should be improved in light of the author's findings and previous literature. Response: Thank you for this valuable suggestion; the discussion section has now been updated. • The authors have not explained any relation between the prediction strategies of different predictors. This should be highlighted in the text. Response: We have used different tools for detecting the pathogenicity of the variations. The relation between the prediction strategies of these predictors has been highlighted in the revised manuscript. • It is necessary to write the reasons why different five proteins were used as the benchmark. Response: Five different proteins were used to avoid any false prediction; only one protein can provide some false positives. Now the reason for this has been updated in the revised manuscript. • In conclusion, the authors write that “Out of the structure-based web tools, mCSM showed a higher number of mutations as destabilizing”. What does it mean? This statement should be elaborated. Response: We have studied only destabilizing/diseased mutations to compare the predictive power of each tool. Here mCSM showed a higher number of mutations as destabilizing means having higher prediction power than others. We have discussed this in more detail during this revision. • The results section is redundant. Please revise, focusing on the specific outcomes and their importance. The strength of the author’s findings should be highlighted. Response: The result section has been updated in light of the reviewers comment. • A uniform presentation is required. The author should proofread the manuscript before final submission. Response: The manuscript has been thoroughly checked and updated during this revised submission. Reviewer #3: Comments to the Authors: 1. Abstract: Can be concise and trim-down; repetitive meanings should be avoided. Response: Thank you for your suggestion. Now the abstract of the manuscript has been updated during this revision. 2. The scientific problem is described well, however, there are a few language mistakes in the text. Therefore, language editing is required to improve the quality of the manuscript. Grammatical mistakes and typographical errors should be corrected. Response: The manuscript has now been thoroughly checked and corrected for typos and language errors. 3. Introduction: Some of the English terminology used is odd which needs to be updated during the revision. Response: Now, the introduction section has been checked for any odd terminology and updated in this revised submission. 4. Introduction, second paragraph, first sentence, needs citation. Response: The citation has now been added to the respective section. 5. The results section has some redundancy in many parts. Authors should update this, focusing on the specific outcomes and their significance. Response: The result section has been revised as per the reviewer's suggestion. We have updated this in a more comprehensive way now. 6. It is not clear how the destabilizing parameters were compared with the values estimated by different tools based on totally different approaches? Response: Each tool gives its score based on some calculations and predicts either a mutation in a protein is destabilizing or not. This has been discussed in the revised submission. 7. The terms deleterious/pathogenic/destabilizing should be described clearly, and their correlations with the prediction should be discussed. Response: Thank you for your suggestion. Now we have described these terms and discussed their correlation with the prediction in the revised submission. 8. Table 1, a column mentioning the reference for the corresponding tool, should be added. Response: Added 9. Discussion should be focused. The author should adhere to the results obtained from experiments. Response: The discussion part of the manuscript has been revised now. 10. Conclusion should be crisp and focused. Outcome must be highlighted in the conclusion section. Conclusions should provide be more details and further highlight the work and its potential importance/application. Response: Thank you for your suggestion. Now we have updated the conclusion of the revised manuscript. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0267084.r002
4 Apr 2022 Decision Letter - Timir Tripathi, Editor Comparative analysis of web-based programs for single amino acid substitutions in proteins PONE-D-21-35921R1 Dear Dr. Hassan, 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, Timir Tripathi, 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 #3: All comments have been addressed ******** 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 #3: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #3: 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 #3: 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: Yes Reviewer #3: 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 all the suggestions and fixed them very well. The revised manuscript should be accepted as is. Reviewer #3: The authors have addressed all the concerns and queries in the manuscript. Accordingly to my review it can be accepted in the current status ****** 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: Yes: Tooba Naz Shamsi Reviewer #3: Yes:** Ethayathulla Abdul Abdul samath https://doi.org/10.1371/journal.pone.0267084.r003
Formally Accepted
25 Apr 2022 Acceptance Letter - Timir Tripathi, Editor PONE-D-21-35921R1 Comparative analysis of web-based programs for single amino acid substitutions in proteins Dear Dr. Hassan: 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. Timir Tripathi Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0267084.r004

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 .