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PONE-D-24-08457PathEX: Make Good Choice for Whole Slide Image ExtractionPLOS ONE

Dear Dr. Yang,

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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Alberto Marchisio

Academic Editor

PLOS ONE

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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: Yes

Reviewer #2: Yes

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

Reviewer #1: No

Reviewer #2: 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: Yes

Reviewer #2: Yes

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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

Reviewer #2: 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: 1.The explanation of BOT in the methodology section is lacking. Compared to IoT, obtaining BOT requires additional algorithms to calculate the area of adipocytes. The main text and pseudocode only contain textual explanations. Please provide more detailed explanations, such as adding formulas and principle explanations. Especially, if using algorithms that have already been developed, they should be referenced, and the contribution should be insufficient.

2.What is the impact of the patch extraction algorithm proposed in this study on downstream tasks? For example, common WSI classification tasks. The author should add comparative experiments in this section to demonstrate the contribution of this study

Reviewer #2: Dear Authors,

Your manuscript titled “PathEX: Make Good Choice for Whole Slide Image Extraction” presents an innovative framework for improving tile image extraction in whole slide image (WSI) analysis. The introduction of Intersection over Tile (IoT) and Background over Tile (BoT) as effective metrics to tackle specific challenges in digital pathology is noteworthy and represents a significant contribution to the field. Below are some comments and suggestions aimed at further strengthening your paper.

While the originality of PathEX are clear, and the note mentioned in the conclusion mentioning that this algorithm is not compared to other methods, the paper would greatly benefit from a more explicit comparison with existing tile extraction methods. In enhancing the comparative analysis of PathEX's performance, algorithms ranging from traditional grid tiling and state-of-the-art DL-based segmentation techniques can be utilized. Moreover, tools like Histolab and SliDL, noted for their specific functionalities in WSI analysis, also serve as good benchmarks. Additionally, evaluating PathEX alongside adaptive tiling methods and any novel, annotation-driven approaches could offer comprehensive insights into its efficacy.

The results section is well-detailed and demonstrates the efficacy of the PathEX algorithm through a variety of metrics. To further bolster these findings, consider including statistical analyses such as p-values or confidence intervals, especially when comparing the performance of different IoT and BoT settings. This would provide a stronger empirical basis for the claims made and help validate the optimal parameter configurations.

The paper touches on the implementation details and the computational resources used, which is appreciated. However, a more thorough discussion on the practical aspects of deploying PathEX, particularly its scalability to larger datasets or its integration into existing digital pathology workflows, would be valuable. Discuss any encountered limitations or challenges and how they might be overcome in future iterations of the framework.

In conclusion, your manuscript makes a valuable contribution to the field of digital pathology. Addressing these points will not only strengthen the paper but also broaden its appeal and applicability. I look forward to seeing the evolution of your work and its impact on the community.

Best regards.

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Reviewer #1: No

Reviewer #2: Yes: Abdul Basit

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PathEX: Make Good Choice for Whole Slide Image Extraction

PONE-D-24-08457R1

Dear Dr. Yang,

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.

Please note that all the minor comments raised by the reviewers should be addressed.

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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Kind regards,

Alberto Marchisio

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 #2: 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: 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

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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

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: Thank you to the authors for the meticulous revisions and improvements made to the manuscript. However, there are still some minor issues that need to be addressed:

1. I recommend adding more recent references to enrich the "related work" section to ensure the timeliness and relevance of the citations. This would not only strengthen the theoretical foundation of your paper but also provide a more comprehensive overview of the latest advancements in the field. Please consider including, but not limited to, the following articles:

-Quan H, Li X, Hu D, et al. Dual-Channel Prototype Network for Few-Shot Pathology Image Classification[J]. IEEE Journal of Biomedical and Health Informatics, 2024.

-Zheng T, Chen W, Li S, et al. Learning how to detect: A deep reinforcement learning method for whole-slide melanoma histopathology images[J]. Computerized Medical Imaging and Graphics, 2023, 108: 102275.

-Ma Y, Luo X, Fu K, et al. Transformer-Based Video-Structure Multi-Instance Learning for Whole Slide Image Classification[C]//Proceedings of the AAAI Conference on Artificial Intelligence. 2024, 38(13): 14263-14271.

By referencing these publications, your paper could more fully reflect the current state of research in the field and potentially draw further inspiration for your studies.

Reviewer #2: Dear Authors,

Thank you for your resubmission of the manuscript titled “PathEX: Make Good Choice for Whole Slide Image Extraction.” I am pleased to inform you that the reviewers comments have been adequately addressed and your work represents a valuable contribution to the field.

I would like to bring to your attention a small edit required on page 9 in Table 2, where the 75th percentile heading is clipping out of the table. Please ensure this formatting issue is corrected for the final version.

Looking forward to your forthcoming publication.

Best regards.

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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

Reviewer #2: Yes: Abdul Basit

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