Preliminary evaluation of a novel nine-biomarker profile for the prediction of autism spectrum disorder

Afaf El-Ansary; Wail M. Hassan; Maha Daghestani; Laila Al-Ayadhi; Abir Ben Bacha

doi:10.1371/journal.pone.0227626

Peer Review History

Original SubmissionSeptember 30, 2019
25 Nov 2019 Decision Letter - Madepalli K. Lakshmana, Editor PONE-D-19-27381 Preliminary evaluation of a novel nine-biomarker profile for the early prediction of autism PLOS ONE Dear Prof El-Ansary, 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 address all the issues raised by the two Reviewers. We would appreciate receiving your revised manuscript by Jan 09 2020 11:59PM. When you are 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. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. 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Please remove your figures from within your manuscript file, leaving only the individual TIFF/EPS image files, uploaded separately. These will be automatically included in the reviewers’ PDF. 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 2 in your text; if accepted, production will need this reference to link the reader to the Table. [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: Partly Reviewer #2: Partly ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: I Don't Know 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: 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) (Limit 200 to 20000 Characters): small sample of both groups gramamtically errors, misspelling Reviewer #2: In the paper “Preliminary evaluation of a novel nine-biomarker profile for the early prediction of autism” by Afaf El-Ansary et al, the authors show that autistic patients can be distinguished from control groups through nine biomarkers, five biomarker ratios, or a combined profile. Although the topic addressed by the authors is of interest given the lack of reliable and early biomarkers for autism, a careful revision of the text to improve the overall quality and the reading of the manuscript. Indeed, many typos, lack of references and inaccuracies are present in all the section. the introduction is poor, some references are inadequate in terms of years of publication and topic for which were mentioned in the text, and some references cited in the text are missing in the list. Specifically 1. in the introduction section - the introduction is poor, some references are inadequate in terms of years of publication and topic for which were mentioned in the text, and some references cited in the text are missing in the list - I would like to suggest to authors to refer to autism as ASD 2. as example of typos in pag 4 - (Beger et al., 2016)) - mytochondrial dysfunction is a well studied in autismd etiological mechanism of autism. in pag 5 in the sentence "oxidative stress, apoptosis, and impaired gut microbiota among other pathoetiological causes. (Ford et al., 2019; El-Ansary., 2016; Castora., 2018). the point before the brackets; the citation El-Ansary., 2016 is correct? in pag 3 this reference is cited as El-Ansary et al in the next sentence there is a repetition "... presenting clinical features of autism at very early age at very early age... in the sentence ... "The diagnosis of ASD was confirmed in all study subjects using the Autism Diagnostic Interview-Revised (ADI-R)..." the acronym for ASD is missing and moreover ASD is better than autism and so on for the entire body of the text 3. I found many inaccuracies in the method and results section as well as in the legends of the figures: - what does means "batches of study population"?? and the sentence "for ...fragile x gene study"? - authors should explain the sentence "all were simplex cases" - Mannervick, 1985 and Beutler, 1963 - many times the authors state "as previously described" but it's wrong - many references are cited as number superscript, why? and so on 4. in the result section - the legend should be after the figure not before - in figure 2, what does means p= 4.2x10-25? p<0.001 should be enough - in fig 4: companion paper? - I suggest a figure to represent the ROC curves - in fig 5, authors state 12 patients while in the rest of text the patients are 13 5.In the discussion section, authors report the results, also referring to table. This is wrong - Since the number of patients enrolled is small, I would suggest to authors to mitigate the sentences concerning the strength of the results obtained, although data are original - many references are missing in the references list: Semmar 2012; Mari et al, 2013 - authors must take into account the form and style with which the references must be cited in the text and reported in the list - authors should improve the discussion with references from other authors, especially concerning the potential use in clinical practice and the role in ASD ethiopathogenesis of the biomarkers 6. in the title "early" is unadequate, the results did not support it ****** 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: 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 to be viewed.] 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 us at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0227626.r001
Revision 1
17 Dec 2019 Author Response Point by point response to Editorial and reviewer’s comments PONE-D-19-27381 Preliminary evaluation of a novel nine-biomarker profile for the early prediction of autism Journal Requirements: 1. When submitting your revision, we need you to address these additional requirements. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. - Done properly 2. Please remove your figures from within your manuscript file, leaving only the individual TIFF/EPS image files, uploaded separately. These will be automatically included in the reviewers’ PDF. - Done and the 5 figures were removed uploaded separately. Figure legends were inserted after the references. 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 2 in your text; if accepted, production will need this reference to link the reader to the Table. - Thanks for this excellent remark. We already referred to Table 2 twice within the text and highlighted in yellow. [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: Partly Reviewer #2: Partly ________________________________________ 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: I Don't Know 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: 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) (Limit 200 to 20000 Characters): -small sample of both groups gramamtically errors, misspelling - Thanks for your comments. Larger samples for both groups well be recruited in the future - The whole manuscript was revised and grammatical and spelling mistakes were corrected along the manuscript ( A certificate is uploaded as supplementary document) Reviewer #2: In the paper “Preliminary evaluation of a novel nine-biomarker profile for the early prediction of autism” by Afaf El-Ansary et al, the authors show that autistic patients can be distinguished from control groups through nine biomarkers, five biomarker ratios, or a combined profile. Although the topic addressed by the authors is of interest given the lack of reliable and early biomarkers for autism, a careful revision of the text to improve the overall quality and the reading of the manuscript. - Careful revision of the whole manuscript was done Indeed, many typos, lack of references and inaccuracies are present in all the section. The introduction is poor, some references are inadequate in terms of years of publication and topic for which were mentioned in the text, and some references cited in the text are missing in the list. - The introduction was improved; multiple updated references relevant to the text were cited (2019&2020). Specifically 1. in the introduction section - the introduction is poor, some references are inadequate in terms of years of publication and topic for which were mentioned in the text, and some references cited in the text are missing in the list - The introduction was improved; multiple updated references relevant to the text were cited (2019&2020). - I would like to suggest to authors to refer to autism as ASD - Done along the manuscript, autism was substituted by ASD 2. as example of typos in pag 4 - (Beger et al., 2016)) - mitochondrial dysfunction is a well studied in autismd etiological mechanism of autism. - Thanks, corrected in pag 5 in the sentence "oxidative stress, apoptosis, and impaired gut microbiota among other pathoetiological causes. (Ford et al., 2019; El-Ansary., 2016; Castora., 2018). The point before the brackets; - Corrected - The citation El-Ansary., 2016 is correct? in pag 3 this reference is cited as El-Ansary et al in the next sentence there is a repetition - Thanks for the excellent remarks. El-Ansary., 2016 is correct but El-Ansary et al., 2016 was missing and up to your comment it was cited in the proper place. "... presenting clinical features of autism at very early age at very early age... - Corrected In the sentence ... "The diagnosis of ASD was confirmed in all study subjects using the Autism Diagnostic Interview-Revised (ADI-R)..."The acronym for ASD is missing and moreover ASD is better than autism and so on for the entire body of the text - Autism was replaced by ASD along the manuscript 3. I found many inaccuracies in the method and results section as well as in the legends of the figures: - What does means "batches of study population"?? and the sentence "for ...fragile x gene study"? - Corrected - Authors should explain the sentence "all were simplex cases" - It was explained - Mannervick, 1985 and Beutler, 1963 - Both are present within the text and listed in the proper place - Many times the authors state "as previously described" but it's wrong - Corrected - Many references are cited as number superscript, why? and so on - Corrected 4. in the result section - the legend should be after the figure not before - Corrected as all figures were deleted and submitted as separate files - In figure 2, what does means p= 4.2x10-25? p<0.001 should be enough - Corrected up to your comment - In fig 4: companion paper? - Removed - I suggest a figure to represent the ROC curves - Figure 5 was constructed and figure’s legends were renumbered accordingly - In fig 5, authors state 12 patients while in the rest of text the patients are 13 - Explained in the Figure legend 5. In the discussion section, authors report the results, also referring to table. This is wrong - Corrected - Since the number of patients enrolled is small, I would suggest to authors to mitigate the sentences concerning the strength of the results obtained, although data are original - many references are missing in the references list: - Semmar 2012 was replaced by more recent reference - Mari et al, 2013 was cited within the list. - The whole list of references was substituted with carefully revised list and rewrittin according to PLOS one guidelines. - authors must take into account the form and style with which the references must be cited in the text and reported in the list - authors should improve the discussion with references from other authors, especially concerning the potential use in clinical practice and the role in ASD ethiopathogenesis of the biomarkers - - Done multiple recent and relevant references were cited within the text and the list 6. in the title "early" is unadequate, the results did not support it - - “Early” was deleted from the title ________________________________________ 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: 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 to be viewed.] 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 us at figures@plos.org. Please note that Supporting Information files do not need this step. ________________________________________ In compliance with data protection regulations, you may request that we remove your personal registration details at any time. (Remove my information/details). Please contact the publication office if you have any questions. Attachments Attachment Submitted filename: Point by point response to PLOS one11-12.docx https://doi.org/10.1371/journal.pone.0227626.r002
26 Dec 2019 Decision Letter - Madepalli K. Lakshmana, Editor Preliminary evaluation of a novel nine-biomarker profile for the prediction of autism spectrum disorder PONE-D-19-27381R1 Dear Dr. El-Ansary, We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements. Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication. Shortly after the formal acceptance letter is sent, an invoice for payment will follow. To ensure an efficient production and billing process, please log into Editorial Manager at https://www.editorialmanager.com/pone/, click the "Update My Information" link at the top of the page, and update your user information. 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 enable them to help maximize its impact. If they will be preparing press materials for this manuscript, you must inform our press team as soon as possible and 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. With kind regards, Madepalli K. Lakshmana, Ph.D Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0227626.r003
Formally Accepted
6 Jan 2020 Acceptance Letter - Madepalli K. Lakshmana, Editor PONE-D-19-27381R1 Preliminary evaluation of a novel nine-biomarker profile for the prediction of autism spectrum disorder Dear Dr. El-Ansary: I am 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 notify them about your upcoming paper at this point, to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, 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. For any other questions or concerns, please email plosone@plos.org. Thank you for submitting your work to PLOS ONE. With kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Madepalli K. Lakshmana Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0227626.r004

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