Interpretable dimensionality reduction and classification of mass spectrometry imaging data in a visceral pain model via non-negative matrix factorization

Kasun Pathirage; Aman Virmani; Alison J. Scott; Richard J. Traub; Robert K. Ernst; Reza Ghodssi; Behtash Babadi; Pamela Ann Abshire

doi:10.1371/journal.pone.0300526

Peer Review History

Original SubmissionJune 3, 2023
26 Jul 2023 Decision Letter - Bardia Yousefi, Editor PONE-D-23-15506Interpretable dimensionality reduction and classification of mass spectrometry imaging data in a visceral pain model via non-negative matrix factorizationPLOS ONE Dear Dr. Abshire, 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 Sep 09 2023 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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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: Partly ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: No ****** 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: Yes 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: Interpretable dimensionality reduction and classification of mass spectrometry imaging data in a visceral pain model via non-negative matrix factorization The authors tried to analyze the Mass spectrometry imaging (MSI) data using non-negative matrix factorization. NMF used to reduce dimensionality and encountering spatial components. In my opinion, this manuscript has these good points: - The subject is interesting and might absorb many readers in the field; - Nice written and well presenting the idea; - Suitable analytical representations; Also, there are some suggestions that would increase the strength of the paper which is listed bellows; - One of my major points about your article concerns the novelty of this article, authors should improve their novelty more highlighted. NMF is used for dimensionality reduction and spectroscopy data analysis (please google this to find more published contributions in the NMF for Hyperspectral, and spectroscopy), what is new in your article. Please specify your contributions. - Why did the size of data shrink from 100K to 20? There should a gap statistic similar approach to justify this. - Similarity to clustering is also needed to the be highlighted and how does this manifest itself into the analysis. Thank you Reviewer #2: In the presentation of the work, the article has a nice beginning; nonetheless, it has to be examined in order to help the reader comprehend “Interpretable dimensionality reduction and classification of mass spectrometry imaging data in a visceral pain model via non-negative matrix factorization." Despite the fact that I believe the work does not satisfy the requirements for publication in PLOS ONE and that there are some concerns that need to be addressed, I strongly propose a comprehensive review that will add value to the results that were acquired through discussion. The writers need to make some changes to the paper. On the other hand, I would like to provide the authors with the following remarks and suggestions: 1. The abstract does not communicate well; it must be revised. 2. In particular, it is not entirely evident how this publication contributes to the body of previous research when compared to other papers that have been published. Because of this, unable to propose that the current version be accepted. 3. In Background and related work section, the author can introduce more literature and analyse its shortcomings to highlight the advantages and innovations of this paper. 4. The results themselves need to be explained, which is why there must be a section or paragraph dedicated to the discussion along with an appropriate comparison table of the suggested work. 5. More specifically, only simulated results were presented, and there was no attempt made to verify the suggested work by practical means in the tabular form. 6. Add some recently proposed techniques (2020-2023) in the related work section of the manuscript. 7. There are too many spelling and grammar mistakes in the paper. It needs proper spelling and grammar checking. 8. Conclusion section should be extended by mentioning the advantages, disadvantages, and limitations of the study. ****** 6. 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Revision 1
30 Oct 2023 Author Response We thank the reviewers for their thoughtful feedback on our manuscript. We have now substantially revised our manuscript by including new analyses, clarifying our results, and improving the clarity and rigor of our expositions. In summary, the major changes include: 1) Adding new analyses to justify the choice of the reduced dimensions (Fig. 4b) and extending the comparison of our proposed approach with existing methods (Fig. 10b and Table 1); 2) Substantially revising the abstract to emphasize the novel contributions of the paper and to be more accessible for a general audience; 3) Clarifying our main contributions in the context of existing recent work, in both the background and discussion sections, and highlighting the advantages, disadvantages, and limitations of our approach; 4) Substantially revising and enhancing the conclusion section; and 5) Improving the rigor and clarity of our presentation by significantly revising the text throughout the manuscript. In what follows, we respond to the comments of the reviewers in a point-by-point fashion. We would like to thank the reviewing editor and the anonymous reviewers for their careful critique of our work and for their constructive and thorough feedback. Reviewer #1: Interpretable dimensionality reduction and classification of mass spectrometry imaging data in a visceral pain model via non-negative matrix factorization The authors tried to analyze the Mass spectrometry imaging (MSI) data using non-negative matrix factorization. NMF used to reduce dimensionality and encountering spatial components. In my opinion, this manuscript has these good points: - The subject is interesting and might absorb many readers in the field; - Nice written and well presenting the idea; - Suitable analytical representations; Response: We thank the reviewer for summarizing the strengths of our contributions. Reviewer #1: Also, there are some suggestions that would increase the strength of the paper which is listed bellows; - One of my major points about your article concerns the novelty of this article, authors should improve their novelty more highlighted. NMF is used for dimensionality reduction and spectroscopy data analysis (please google this to find more published contributions in the NMF for Hyperspectral, and spectroscopy), what is new in your article. Please specify your contributions. Response: We thank the reviewer for raising this point on clarifying the novelty of our work. We have now revised our abstract to clarify the main contributions of the work as being three novel MSI data analysis techniques that leverage the spatial and spectral interpretability of NMF compressed MSI data (pp. 1 - 2). We also added a section highlighting the connection to existing work in MSI data analysis to highlight the novel aspects of this work (pp. 5 - 6). Reviewer #1: - Why did the size of data shrink from 100K to 20? There should a gap statistic similar approach to justify this. Response: We are not performing a traditional clustering, so gap statistics are not readily available or well defined for this approach. Instead we set a target error rate of 20% in reconstruction accuracy and used this criterion to select the number of components to retain in subsequent analysis. We have now revised Fig 4 to clearly show the selection criterion for the reduced dimension (for both PCA and NMF) (pp. 13) Reviewer #1: - Similarity to clustering is also needed to the be highlighted and how does this manifest itself into the analysis. Response: One of the key findings in this work is that NMF inherently produces components with spatially distinct structure obviating the need for an additional explicit clustering step. We have now added this explanation to the section on review of existing MSI data processing methods (pp. 5 - 6). Reviewer #2: In the presentation of the work, the article has a nice beginning; nonetheless, it has to be examined in order to help the reader comprehend “Interpretable dimensionality reduction and classification of mass spectrometry imaging data in a visceral pain model via non-negative matrix factorization." Despite the fact that I believe the work does not satisfy the requirements for publication in PLOS ONE and that there are some concerns that need to be addressed, I strongly propose a comprehensive review that will add value to the results that were acquired through discussion. The writers need to make some changes to the paper. On the other hand, I would like to provide the authors with the following remarks and suggestions: Response: We thank the reviewer for their careful critique of our work and for providing a number of insightful suggestions to improve it. Reviewer #2: 1. The abstract does not communicate well; it must be revised. Response: We have now revised our abstract to clarify the main contributions of the work as being three novel MSI data analysis techniques that leverage the spatial and spectral interpretability of NMF compressed MSI data (pp. 1 - 2). Reviewer #2: 2. In particular, it is not entirely evident how this publication contributes to the body of previous research when compared to other papers that have been published. Because of this, unable to propose that the current version be accepted. Response: As noted above, we have now revised the abstract to better communicate the novelty of our work (pp. 1 - 2). We have also added a more thorough literature review, specifically highlighting the novelty of our work in terms of NMF as it applies to downstream MSI data processing (pp. 5 - 6). Reviewer #2: 3. In Background and related work section, the author can introduce more literature and analyze its shortcomings to highlight the advantages and innovations of this paper. Response: We have now added a more thorough literature review, specifically highlighting the novelty of our work on NMF data compression as it applies to downstream MSI data processing. We have also emphasized how our work relates to existing approaches (pp. 5 - 6). Reviewer #2: 4. The results themselves need to be explained, which is why there must be a section or paragraph dedicated to the discussion along with an appropriate comparison table of the suggested work. Response: We have added subheadings in the discussion section to highlight the material related to results for distinct topics in our paper and improve readability. (pp. 22- 25) Since the novelty of our work lies in data processing methodologies (i.e., how to integrate NMF into data processing pipelines for downstream analyses), it is hard to perform a quantitative comparison with other methods. To establish a benchmark for how NMF and PCA perform on the novel dataset used in this work, we have added a table illustrating the comparison of PCA and NMF results on this novel dataset (pp. 22). We have also modified Fig 10 to show how the methodologies described in this paper, when applied to NMF compressed MSI data, compare against MSI data compressed with PCA. (pp. 21) Reviewer #2: 5. More specifically, only simulated results were presented, and there was no attempt made to verify the suggested work by practical means in the tabular form. Response: All of the results in this paper are based on a novel MSI dataset obtained from an animal model of comorbid visceral pain hypersensitivity, which is described in the Animal Model, Tissue Preparation, Mass spectrometry imaging and staining, and Datasets sections (pp. 7-9), We have reworded the abstract to emphasize the novelty of this dataset that we use for validating the methods (pp. 1 - 2). As noted above, we have also added a table comparing PCA and NMF approaches as applied to this novel dataset (pp. 22). Reviewer #2: 6. Add some recently proposed techniques (2020-2023) in the related work section of the manuscript. Response: We have added a section on MSI data processing highlighting recent contributions and their connection to this work. We have updated the bibliography with the respective literature (references 21 - 24) (pp. 5 - 6). Reviewer #2: 7. There are too many spelling and grammar mistakes in the paper. It needs proper spelling and grammar checking. Response: We have thoroughly proofread the manuscript for spelling and grammatical mistakes and have resolved all issues that we found. Reviewer #2: 8. Conclusion section should be extended by mentioning the advantages, disadvantages, and limitations of the study. Response: We have significantly expanded the conclusion, describing in detail the advantages, disadvantages and limitations of our study (pp. 25 - 26). Attachments Attachment Submitted filename: Response_to_Reviewers_PONE-D-23-15506R1.docx https://doi.org/10.1371/journal.pone.0300526.r002
29 Feb 2024 Decision Letter - Bardia Yousefi, Editor Interpretable dimensionality reduction and classification of mass spectrometry imaging data in a visceral pain model via non-negative matrix factorization PONE-D-23-15506R1 Dear Dr. Abshire, 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, Bardia Yousefi, Ph.D. Academic Editor PLOS ONE Additional Editor Comments (optional): Authors responded well to the comments received. I recommend accepting this manuscript Congratulations 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 ******** 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 ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: 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 ****** 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 ****** 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: Authors responded well to my comments. Particularly respond to the novelty was sufficient. I don't have any comments. ****** 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 ******** https://doi.org/10.1371/journal.pone.0300526.r003
Formally Accepted
21 Mar 2024 Acceptance Letter - Bardia Yousefi, Editor PONE-D-23-15506R1 PLOS ONE Dear Dr. Abshire, 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. Bardia Yousefi Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0300526.r004

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