PONE-D-24-07162Signals of Complexity and Fragmentation in accelerometer dataPLOS ONE

Dear Dr. Weinans,

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.

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ACADEMIC EDITOR:

1. The authors are advised to provide more details on parameter selection in the methods section and discuss how these choices affect the results.

2. Further discussion on the finding that a lower correlation dimension may imply a more predictable pattern is recommended.

3.The potential clinical implications of these findings should be explored.

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Kind regards,

Yunhe Wang

Academic Editor

PLOS ONE

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Additional Editor Comments:

1.The authors are advised to provide more details on parameter selection in the methods section and discuss how these choices affect the results.

2.Further discussion on the finding that a lower correlation dimension may imply a more predictable pattern is recommended.

3.The potential clinical implications of these findings should be explored.

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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: No

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

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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: No

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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

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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: Dear Authors,

I recently had the opportunity to read your manuscript and found it intriguing, particularly from a complex systems perspective. However, I have some major concerns regarding certain technical and methodological aspects. My major concerns are outlined below.

• The sample size used for the main analysis (cross-sectional, as far as I understand from the manuscript) is very small. Additionally, one group was observed for 2 weeks, while the other group was observed for only 1 week. The sample sizes of the two groups are also notably imbalanced. The U statistic from the Mann-Whitney test is calculated based on the ranks of the combined groups. When one group is much larger, the ranks of the smaller group are spread thinly across the larger group’s ranks, which can bias the results. Finally, no power analysis was performed. While I understand that this was a convenience sample used to test the research questions, these limitations raise concerns about the reliability of the current findings.

• Higher correlations are likely descriptive of the symptoms that characterize the DM1 group—and the broader population with myotonic dystrophy type 1—rather than being indicators capable of distinguishing between groups with known health differences. Specifically, from the protocol paper (van Engelen, 2015), I understand that this population is characterized by daytime sleepiness. Therefore, one might assume that the highly irregular signals in the DM1 group are due to this condition. On a related note, in line 370 (page 15), the authors state that "Healthy individuals had several consecutive hours of low activity every 24 hours, whereas individuals with DM1 had multiple periods of low activity scattered throughout the day and night (linking to their high active-to-rest transition probability). Whereas previous studies have chosen to remove periods of sleep [9], the complicated sleep pattern of the DM1 group did not allow us to follow this approach." The fact that the complex sleep patterns prevented the authors from removing sleep periods further supports my view that the high correlation in accelerometer data might be typical of this clinical sample, rather than indicative of a generic unhealthy population. A different comparator is needed to assess the discriminative value of the correlation measures to distinguish between groups with known health differences.

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Reviewer #1: No

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PONE-D-24-07162R1Signals of Complexity and Fragmentation in accelerometer dataPLOS ONE

Dear Dr. Weinans,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by May 25 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,

Sandip V George, PhD

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:

Dear Authors,

I was reassigned to this paper as academic editor. Since I am aware of the significant delays in processing this manuscript, I do not intent to send this out to additional reviewers. I do have some concerns about the manuscript, which I would like to be seen addressed in a revision. These are mostly methodological.

1. As the reviewer pointed out, the control sample lasted a week less than the DM1 sample. Correlation dimension is well known to be affected by sample length. Have the authors already checked if reducing the sample size to a week affects the differences observed? If not this would be worth investigating

2. I checked the github repo to check the above, but noticed that the code used for calculating the complexity measures were not available. Could this be added to the repo?

3. I understand that the authors interpret correlation dimension in the context of random data, but since the measure is originally developed for the analysis of signals exhibiting deterministic chaos, it would be nice to have an interpretation of what that is. In the supplementary, the authors have considered purely deterministic signals as well for their analysis. While it is generally true that regularity implies lower dimension and randomness or chaos implies higher dimensions, Correlation dimension is in essence a measure of fractality. I would recommend adding a few lines describing what exactly it is measuring in the paper, especially since a lot of the readers may be non-specialists.

4. Choice of tau=1: While in theory Taken's theorem guarantees that any value of delay time, tau, will work, for real datasets it is recommended that a delay time where the correlation (linear or otherwise) decays is chosen. Common thresholds are where the autocorrelation falls to 1/e or first minimum of the mutual information etc. It would be worthwhile to consider adding a sensitivity analysis that looks into these.

5. Choice of dimension: The authors chose dimension of 6 as far as I understand. But I don't understand Figure 6. Is this the dimension that was obtained at dimension 6? This seems unlikely, since there was no saturation observed for DM1, according to the authors. Maybe it would be worthwhile to add average D2 at every dimension for the healthy and diseased datasets in the main text/supplementary. In addition, if D2(1/2), i.e. correlation dimension at dimension 1 or 2, was chosen for the analysis, this may not be the best choice, since at this dimension the full complexity of the embedded space will not be captured by the measure.

6. Choice of threshold for transition probability analysis. Its set currently via visual inspection. Is this number close to a number that can be objectively defined? n times mean/median/standard deviation. What would be a suitable recommendation for future researchers looking to repeat this analysis for their datasets?

7. Saturation curves for example datasets: In the supplementary data, the authors provide C(R) vs R curves for the data. It would make sense to add D2(M) vs M curves as well, i.e. Correlation dimension vs dimension curves. This would make the saturation observed in the healthy controls evident.

8. Figure 11 in supplementary will be clearer if plotted using points alone. The lines obscure the structure.

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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

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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: Partly

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

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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

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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

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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: I thank the authors for their responses to my comments. They have been clearer and more transparent about the limitations of the study. However, in my view, one of these limitations (as highlighted in my second comment during the first review round regarding the use of a different comparator) remains "unresolved." This is because the study relied on a convenience sample, and no other unhealthy comparators are available. While the authors have acknowledged this as a limitation, I remain concerned that the conclusions may be biased.

That said, given the overall rigor, novelty, and thorough documentation of the analysis, I am inclined to leave it to the editor to decide whether this limitation warrants acceptance or rejection of the article.

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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: No

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[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.

Signals of Complexity and Fragmentation in accelerometer data

PONE-D-24-07162R2

Dear Dr. Weinans,

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.

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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,

Sandip V George, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

The authors have addressed all my queries.

Reviewers' comments: