The Association between PTPN22 SNPs and susceptibility to type 1 diabetes: An updated meta-analysis

Yu Su; Xue Li; Pei-dong Wu; Yu-long Zhang; Peng-fei Fang; Fei-fei Wu; Xiao-feng He

doi:10.1371/journal.pone.0321624

Peer Review History

Original SubmissionNovember 4, 2024
4 Nov 2024 Author Response https://doi.org/10.1371/journal.pone.0321624.r001
26 Dec 2024 Decision Letter - Petr Heneberg, Editor PONE-D-24-50318The Association between PTPN22 SNPs and Susceptibility to Type 1 Diabetes: An updated meta-analysisPLOS ONE Dear Dr. Wu, 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 09 2025 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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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: This manuscript reports and interesting meta-analysis of the association of PTPN22 SNPs and susceptibility to type 1 diabetes. The manuscript should be completed by an indept analysis when possible of the frequency of the SNPs in different populations where these data have not been evaluated The manuscript requires revision by a native english speaker. I would revise the sentence in the abstract 'the findings regarding the relationship between SNPs and T1D susceptibility have been inconsistent'. Studies indeed were 'not conclusive in different populations' while in some such as the Italian or caucasian populations the frequency has been extimated and found significant in diabetics at least for the C1858T SNP Reviewer #2: The Manuscript sounds interesting and cover all aspects and I would suggest a minor revision to improve the discussion section more with slightly grammarly and English improvment while the data is correctly addressed and conclsuion you can add 2 3 lines more. ****** 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: No Reviewer #2: Yes: Sammra Maqsood ******** [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: PONE-D-24-50318.pdf https://doi.org/10.1371/journal.pone.0321624.r002
Revision 1
19 Feb 2025 Author Response Dear PLOS ONE Staff, On behalf of all co-authors, I sincerely appreciate your constructive feedback and the opportunity to revise our manuscript titled "The Association between PTPN22 SNPs and Susceptibility to Type 1 Diabetes: An updated meta-analysis" (manuscript number: PONE-D-24-50318). We have carefully addressed each point raised in your review and detailed our responses below. Revised sections are marked in the manuscript, and supplementary files have been updated accordingly. 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 Response: Thank you for providing the Author Formatting Checklist to ensure that our paper meets PLOS ONE's typesetting requirements for References, Tables, and Figures. We will carefully review the checklist and make the necessary adjustments to our submission files accordingly. 2.We note that your Data Availability Statement is currently as follows: [We gratefully acknowledge the contributors to all the original studies included in this meta-analysis.] Please confirm at this time whether or not your submission contains all raw data required to replicate the results of your study. Authors must share the “minimal data set” for their submission. PLOS defines the minimal data set to consist of the data required to replicate all study findings reported in the article, as well as related metadata and methods (https://journals.plos.org/plosone/s/data-availability#loc-minimal-data-set-definition). For example, authors should submit the following data: - The values behind the means, standard deviations and other measures reported; - The values used to build graphs; - The points extracted from images for analysis. Authors do not need to submit their entire data set if only a portion of the data was used in the reported study. If your submission does not contain these data, please either upload them as Supporting Information files or deposit them to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. For a list of recommended repositories, please see https://journals.plos.org/plosone/s/recommended-repositories. If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially sensitive information, data are owned by a third-party organization, etc.) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent. If data are owned by a third party, please indicate how others may request data access. Response: We confirm that our submission includes all raw data required to replicate the results of our study. The data has been provided in the supplementary materials as per the journal’s requirements(Supporting Information files). 3.PLOS requires an ORCID iD for the corresponding author in Editorial Manager on papers submitted after December 6th, 2016. Please ensure that you have an ORCID iD and that it is validated in Editorial Manager. To do this, go to ‘Update my Information’ (in the upper left-hand corner of the main menu), and click on the Fetch/Validate link next to the ORCID field. This will take you to the ORCID site and allow you to create a new iD or authenticate a pre-existing iD in Editorial Manager. Response: The ORCID iD of the corresponding author (Fei-fei Wu: 0009-0000-0333-9833) has been added to the title page and verified in Editorial Manager. 4.Please include a new copy of Tables in your manuscript; the current table is difficult to read. Please follow the link for more information: https://blogs.plos.org/plos/2019/06/looking-good-tips-for-creating-your-plos-figures-graphics/ Response: All tables (Tables 1-5) have been reformatted using Arial font for clarity. Headings have been bolded for better differentiation and improved readability. The updated tables are included in the manuscript and in the supplementary document. 5.As required by our policy on Data Availability, please ensure your manuscript or supplementary information includes the following: A numbered table of all studies identified in the literature search, including those that were excluded from the analyses. For every excluded study, the table should list the reason(s) for exclusion. If any of the included studies are unpublished, include a link (URL) to the primary source or detailed information about how the content can be accessed. A table of all data extracted from the primary research sources for the systematic review and/or meta-analysis. The table must include the following information for each study: Name of data extractors and date of data extraction Confirmation that the study was eligible to be included in the review. All data extracted from each study for the reported systematic review and/or meta-analysis that would be needed to replicate your analyses. If data or supporting information were obtained from another source (e.g. correspondence with the author of the original research article), please provide the source of data and dates on which the data/information were obtained by your research group. If applicable for your analysis, a table showing the completed risk of bias and quality/certainty assessments for each study or outcome. Please ensure this is provided for each domain or parameter assessed. For example, if you used the Cochrane risk-of-bias tool for randomized trials, provide answers to each of the signalling questions for each study. If you used GRADE to assess certainty of evidence, provide judgements about each of the quality of evidence factor. This should be provided for each outcome. An explanation of how missing data were handled. This information can be included in the main text, supplementary information, or relevant data repository. Please note that providing these underlying data is a requirement for publication in this journal, and if these data are not provided your manuscript might be rejected. Response: Thank you for reviewing our work and providing valuable feedback. We fully acknowledge the importance of including a list of excluded studies to enhance transparency and reproducibility. Excel files containing all relevant data, such as the names of data extractors, extraction dates, eligibility criteria, and the necessary information for replication, are provided in the Supporting Information files. Furthermore, a table summarizing the risk of bias and quality assessments for each study or outcome is included (Table S2). The manuscript also contains a detailed explanation of the methods used to address missing data. 6.The manuscript should be completed by an indept analysis when possible of the frequency of the SNPs in different populations where these data have not been evaluated Response: Thank you for your valuable feedback on our study. We noted the observed discrepancies between the SNP frequencies in our study and those reported in the HapMap and 1000 Genomes Project databases (Supplemental Table 4). We believe these discrepancies may stem from several factors: First, HapMap primarily reflects population frequencies under broad ethnic classifications, whereas our current study focuses on specific case-control cohorts. Genetic drift, founder effects, and subpopulation differences within ethnic groups may contribute to variations in allele frequencies. Second, the higher T allele frequency observed in our case group supports the role of rs2476601 as a susceptibility locus for type 1 diabetes (T1D), while the slight enrichment in the control group may suggest the presence of undiagnosed autoimmune conditions. Additionally, differences in sample size, genotyping methodologies, and environmental selection pressures could further explain the observed frequency variations. We agree with your suggestion that future studies involving larger and more diverse populations are needed to validate our findings and to further elucidate the genetic basis of T1D susceptibility. We have incorporated these explanations into the Discussion section and addressed additional limitations to enhance the clarity and context of our findings. We sincerely appreciate your constructive comments and thank you again for your insights. 7.The manuscript requires revision by a native english speaker. I would revise the sentence in the abstract 'the findings regarding the relationship between SNPs and T1D susceptibility have been inconsistent'. Studies indeed were 'not conclusive in different populations' while in some such as the Italian or caucasian populations the frequency has been extimated and found significant in diabetics at least for the C1858T SNP. Response: The manuscript has been thoroughly edited by a native English speaker. The abstract sentence now reads: "Studies investigating the relationship between PTPN22 rs2476601 and T1D risk have consistently demonstrated an association in certain populations, whereas research on rs1310182 has yielded conflicting and less conclusive results. " Additional grammatical improvements have been made throughout the manuscript, and track changes have been used to mark edits for clarity. 8.The Manuscript sounds interesting and cover all aspects and I would suggest a minor revision to improve the discussion section more with slightly grammarly and English improvment while the data is correctly addressed and conclsuion you can add 2 3 lines more. Response: We appreciate the positive feedback. The Discussion section has been revised for clarity and grammatical accuracy. We have also expanded the Conclusion section to further emphasize the significance of our findings. Specifically, we added 2–3 lines to highlight the potential implications of our study for understanding genetic contributions to T1D and the importance of population-specific research. 9.PLOS authors have the option to publish the peer review history of their article . If published, this will include your full peer review and any attached files. Response: We understand this option and will consider publishing the peer review history after the final acceptance of the manuscript. 10.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. Response: We thank you for suggesting that we use the PACE tool to ensure that our data meets the technical requirements of PLOS ONE. Following the instructions provided, we have performed the necessary evaluation and conversion of our graphical files to meet the journal's specifications. Thank you for your detailed feedback and guidance. We hope that the revised manuscript meets the journal’s requirements. Please do not hesitate to contact us if further modifications are required. Kind regards, Fei-fei Wu Attachments Attachment Submitted filename: Response to Editor.docx https://doi.org/10.1371/journal.pone.0321624.r003
28 Feb 2025 Decision Letter - Petr Heneberg, Editor PONE-D-24-50318R1The Association between PTPN22 SNPs and Susceptibility to Type 1 Diabetes: An updated meta-analysisPLOS ONE Dear Dr. Wu, 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 Apr 14 2025 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, Petr Heneberg 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. Additional Editor Comments: - Tables 1 and 2 - Zak et al. 2023 examined patients from Armenia, not from America. - Fig 2 - state clearly the reasons for exlusion of studies explicitly mentioned in the figure. - Fig. 1 - typo "titlis". - The whole study needs to better reflect the geographic gradient of the study polymorphisms within the Caucasian populations. There are enormous differences in the prevalence of the study rs in general and T1DM Caucasian populations both in the N-S and E-W directions throughout Europe. It is described the best for rs2476601. These differences are enormous and prevent generalization of conclusions for the whole Caucasian population. - I cannot open the supplementary files. Please double-check their integrity and reupload them. [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: All comments have been addressed Reviewer #2: 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 #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: Yes 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 manuscript can be accepted in the present revised version. The authors have satisfactorely replied to the reviewers'comments and criticism Reviewer #2: The author addressed all the comments and I highly recommend for the submission and all the points are addressed. ****** 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: Alessandra Fierabracci Reviewer #2: Yes: Sammra Maqsood ******** [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.0321624.r004
Revision 2
8 Mar 2025 Author Response Dear PLOS ONE Staff, On behalf of all co-authors, I sincerely appreciate your constructive feedback and the opportunity to revise our manuscript titled "The Association between PTPN22 SNPs and Susceptibility to Type 1 Diabetes: An updated meta-analysis" (manuscript number: PONE-D-24-50318). We have carefully addressed each point raised in your review and detailed our responses below. Revised sections are marked in the manuscript, and supplementary files have been updated accordingly. 1.Tables 1 and 2 - Zak et al. 2023 examined patients from Armenia, not from America. Response: We thank the editor for bringing this error to our attention. The geographic origin of the study population in Tables 1 and 2 has been corrected accordingly. Zak et al. (2023) is now accurately described as examining patients from Armenia. 2.Fig 2 - state clearly the reasons for exlusion of studies explicitly mentioned in the figure. Response: We appreciate the suggestion to improve clarity. In the manuscript, we have clearly outlined the specific reasons for excluding certain studies. These reasons include studies with quality scores ≤12 and studies related to HWD. Additionally, to enhance transparency, we have provided a detailed explanation of the exclusion criteria in the Quality Assessment section of the manuscript 3.Fig. 1 - typo "titlis". Response: We thank the editor for pointing out this typographical error. The word "titlis" in Figure 1 has been corrected to "titles." Additionally, we have thoroughly reviewed the manuscript and figures to identify and correct any other typographical errors, ensuring the accuracy of the content. 4.The whole study needs to better reflect the geographic gradient of the study polymorphisms within the Caucasian populations. There are enormous differences in the prevalence of the study rs in general and T1DM Caucasian populations both in the N-S and E-W directions throughout Europe. It is described the best for rs2476601. These differences are enormous and prevent generalization of conclusions for the whole Caucasian population. Response: We thank the editors for their valuable comments regarding the need to consider geographic differences in the prevalence of the studied polymorphisms within Caucasian populations. In response, we have significantly revised the manuscript and Table 3 to address this concern. Specifically: We excluded mixed-race populations and performed subgroup analyses based on geographic regions (Eastern, Western, Northern, Southern, and Central Europe). Our forest plots and heterogeneity analyses revealed notable regional variations in effect sizes. Heterogeneity was highest in Southern Europe (I² = 63.2%, p = 0.028) and moderate in Western Europe (I² = 59.3%, p = 0.086). In contrast, Eastern, Northern, and Central Europe exhibited minimal heterogeneity (I² = 0.0–10.5%, p > 0.3). The overall analysis demonstrated a significant correlation (z = 8.60, p < 0.001), consistent with findings from most regions. However, the results for Southern Europe were not statistically significant (z = 1.23, p = 0.217), potentially reflecting differences in population structure or allele frequencies. These findings underscore the importance of accounting for geographic differences when interpreting genetic associations in Caucasian populations and further support the robustness of our conclusions for most regions. We have further discussed these differences and their implications in the revised discussion section of the manuscript. 5.I cannot open the supplementary files. Please double-check their integrity and reupload them. Response: We apologize for the inconvenience caused by the issues with the supplementary files. The supplementary information file has been re-uploaded with the following adjustments: it has been converted to the Excel 97-2003 (.xls) format for broader compatibility, and its integrity has been verified using LibreOffice 25.2.1 and WPS Office. If the issue persists, we would be happy to provide the files in alternative formats (e.g., PDF or CSV). Thank you for your detailed feedback and guidance. We hope that the revised manuscript meets the journal’s requirements. Please do not hesitate to contact us if further modifications are required. We look forward to your response. Kind regards, Fei-fei Wu Attachments Attachment Submitted filename: Response_to_Editor_auresp_2.docx https://doi.org/10.1371/journal.pone.0321624.r005
11 Mar 2025 Decision Letter - Petr Heneberg, Editor <p>The Association between PTPN22 SNPs and Susceptibility to Type 1 Diabetes: An updated meta-analysis PONE-D-24-50318R2 Dear Dr. Wu, 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, Petr Heneberg Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0321624.r006
Formally Accepted
Acceptance Letter - Petr Heneberg, Editor PONE-D-24-50318R2 PLOS ONE Dear Dr. Wu, 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. Petr Heneberg Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0321624.r007

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