PCOMPBIOL-D-25-00816

LC-Inspector: a simple open-source viewer for targeted hyphenated mass spectrometry analysis

PLOS Computational Biology

Dear Dr. Slack,

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Mohammad Sadegh Taghizadeh, Ph.D.

Academic Editor

PLOS Computational Biology

Shihua Zhang

Section Editor

PLOS Computational Biology

Additional Editor Comments :

Please note that the comments from Reviewer #1 has been attached.

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4) We notice that you stated "LC-Inspector is distributed under the MIT license. The source code and executables for Windows and MacOS, as well as installation instructions, can be found free of charge on GitHub (https://github.com/MateuszFido/LC-Inspector). Version 0.3 (designed to be run on a high-performance computing cluster) can be downloaded from Zenodo (DOI: https://doi.org/10.5281/zenodo.13990448)" under the heading "SUPPORTING INFORMATION." Please note that supplementary information should not be included in the manuscript file. It should be uploaded separately with the file type 'Supporting Information'. If this is not supplementary information, please amend the heading accordingly.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Authors:

Please note that one of the reviews is uploaded as an attachment.

Reviewer #1: The authors did a great job on this manuscript LC-Inspector: a simple open-source viewer for targeted hyphenated mass spectrometry analysis to PLOS Computational Biology. The development of LC-Inspector is a commendable contribution to the mass spectrometry community, particularly in providing an accessible, user-friendly, and open-source tool for non-experts in the field. I have carefully reviewed your manuscript and would like to provide some constructive feedback to help improve its clarity and overall impact.

Reviewer #2: Fido et al. present LC-Inspector, which seems to be a useful utility for hyphenated MS data analysis. The manuscript is fairly straightforward in describing the software and its capabilities. I think the work is sound and I have no major critique. My rather minor comments below:

p2:32 (and elsewhere)

The abbreviation MS has already been introduced, so use it consistently instead of ‘mass spectrometry’.

p2:39

“vendor’s” should probably be “vendors’” because plural genitive.

p3:55

“LC-Inspector is a completely free-of-charge…” Note that LC-Inspector has not been introduced yet. Consider “Here, we present LC-Inspector, which is a completely free-of-charge…”

p3:64

“...concurrency and futures modules.” I suspect the authors mean “…concurrency.future modules”. Unless there coincidentally is a separate futures module that I cannot find.

p3:72-47

Text or csv files can have their data stored in many ways. If certain column orders or similar are expected, please mention that.

p4:85

“It then rebuilds the extracted ion chromatograms for those m/z ranges…” Maybe it is a convention I am unfamiliar with, or I misunderstand something, but is the term ‘ion chromatogram’ used for ions in a mass spectrometer? If so, fine, but if not, I suggest referring to it by another name, like a reduced mass spectrum or something. Especially since chromatography data is also part of the context. If I misunderstand, at least consider that the text can be misinterpreted as it is currently written.

p4:96

“comma-separated values (CSV)” CSV has already been discussed, so no point in introducing the abbreviation here.

p7:145

It would be prudent to cite the original paper Hampton et al. (https://doi.org/10.1016/0168-9002(94)91657-8) in relation to the LLS operator.

Lastly, I am curious about the name of the software. LC suggests liquid chromatography, but the central technique here is MS. Is there some history behind the name?

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Have the authors made all data and (if applicable) computational code underlying the findings in their manuscript fully available?

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes:  Shafiu A. Umar Shinge

Reviewer #2: No

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Submitted filename: Reviewer report.docx

PCOMPBIOL-D-25-00816R1

LCMSpector: a simple open-source viewer for targeted hyphenated mass spectrometry analysis

PLOS Computational Biology

Dear Dr. Slack,

Thank you for submitting your manuscript to PLOS Computational Biology. After careful consideration, we feel that it has merit but does not fully meet PLOS Computational Biology'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 within 30 days (November 09, 2025, at 23:59). If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at ploscompbiol@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pcompbiol/ 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 editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. This file does not need to include responses to formatting updates and technical items listed in the 'Journal Requirements' section below.

* 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, competing interests statement, or data availability statement, please make these updates within the submission form at the time of resubmission. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

We look forward to receiving your revised manuscript.

Kind regards,

Mohammad Sadegh Taghizadeh, Ph.D.

Academic Editor

PLOS Computational Biology

Shihua Zhang

Section Editor

PLOS Computational Biology

Journal Requirements:

If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise.

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2) Some material included in your submission may be copyrighted. According to PLOSu2019s copyright policy, authors who use figures or other material (e.g., graphics, clipart, maps) from another author or copyright holder must demonstrate or obtain permission to publish this material under the Creative Commons Attribution 4.0 International (CC BY 4.0) License used by PLOS journals. Please closely review the details of PLOSu2019s copyright requirements here: PLOS Licenses and Copyright. If you need to request permissions from a copyright holder, you may use PLOS's Copyright Content Permission form.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Authors:

Please note here if the review is uploaded as an attachment.

Reviewer #1: Dear Authors,

I have carefully examined your point-by-point responses and the revised manuscript. I am pleased to note that you have been exceptionally responsive and have undertaken a comprehensive revision that has substantially elevated the quality, rigor, and impact of your work. The additions and clarifications have effectively mitigated the core concerns I have raised in the initial review.

Specifically, the following revisions are particularly noteworthy and have enhanced the manuscript from a promising software description into a convincing and validated resource for the community

1. Introduction of rigorous performance benchmarks, the authors addition of head-to-head performance comparisons with established tools like MZmine and OpenMS TOPPView (Figure 5C-E) is a critical improvement. By quantifying loading times, processing speed, and memory footprint across three operating systems, you have moved beyond qualitative claims of efficiency to provide concrete, empirical evidence. The finding that LCMSpector achieves competitive speed while consuming significantly less memory is a strong and distinct advantage that you have now convincingly demonstrated.

2. Validation of quantitative fidelity against a gold standard, the manuscript quantitative analysis comparing LCMSpector's concentration estimates against those from the vendor's own algorithm (Chromeleon) and MZmine (Figure 5A-B) is exactly the type of validation required to build trust in a new analytical tool. The results, which intriguingly show superior performance of the open-source tools in this specific direct-infusion context, provide a powerful argument for the accuracy and reliability of your software's core algorithms.

3. Demonstration of biological utility through a case study, the authors new analysis of a published liver disease dataset (Figure 3) successfully bridges the gap between technical capability and biological discovery. This no longer feels like a simple demonstration, but an actual research application. The insight regarding the potential impact of dimer peaks on bile acid quantification is a perfect example of how your software's integrated, raw-data-viewing capability can lead to more accurate and insightful analyses a key selling point that is now powerfully substantiated.

4. Empirical support for user-friendliness, conducting a formal usability study (Figure 6) was an excellent initiative that moves discussions of the GUI from anecdotal to evidence-based. The positive feedback from novice users provides robust, independent validation of your central thesis: that LCMSpector successfully lowers the barrier to entry for complex MS data analysis.

5. Enhanced scholarly transparency and reproducibility, the authors’ inclusion of a dedicated ‘Limitations’ section, a future development roadmap (Fig. S2), and the freezing of the code version with a specific commit hash and Zenodo DOI represent best practices in open-source software publication. This level of transparency not only builds immediate credibility but also thoughtfully sets community expectations and facilitates future collaboration and development.

6. Improved conceptual and algorithmic clarity, the restructuring of the SNIP algorithm explanation into a step-by-step process and the detailed computational analysis of the XIC construction algorithm greatly enhance the manuscript's educational value and clarify the novel contributions of your implementation, effectively distinguishing it from a mere repackaging of existing libraries.

Despite the revisions are excellent, two minor points could be considered

1. The response letter mentions increasing test coverage to ‘about 90%’. For maximum transparency, the exact test coverage percentage could be included in the "Availability" section or the GitHub repository.

2. The stability issues noted in the usability study (crashes during simultaneous operations) are acknowledged as a point for future improvement. While it's good they are noted, a brief sentence in the ‘Limitations’ section could further demonstrate transparency.

The authors have undertaken a rigorous and highly effective revision process. They have responded to all my comments and significantly enhanced the scientific rigor, clarity, and impact of their work through the addition of extensive new data and analyses. The manuscript now provides convincing evidence for the performance, accuracy, and user-friendliness of LCMSpector, effectively positioning it as a valuable new open-source tool for targeted mass spectrometry analysis.

The revisions have fully addressed all my major and minor concerns. The manuscript now meets the high standards expected for a software publication in PLOS Computational Biology. The manuscript is now ready to proceed further for the Editor-in-Chief’s final decision.

Reviewer #2: The authors have reacted and responded to the comments from both reviewers in an adequate and satisfying way. I see no reason not to accept for publication.

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Have the authors made all data and (if applicable) computational code underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data and code 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 and code 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 or code —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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Reviewer #1: Yes:  SHAFIU A. UMAR SHINGE

Reviewer #2: No

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Reproducibility:

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Submitted filename: Reviewer comment .docx

Dear Dr. Slack,

We are pleased to inform you that your manuscript 'LCMSpector: a simple open-source viewer for targeted hyphenated mass spectrometry analysis' has been provisionally accepted for publication in PLOS Computational Biology.

Before your manuscript can be formally accepted you will need to complete some formatting changes, which you will receive in a follow up email. A member of our team will be in touch with a set of requests.

Please note that your manuscript will not be scheduled for publication until you have made the required changes, so a swift response is appreciated.

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Thank you again for supporting Open Access publishing; we are looking forward to publishing your work in PLOS Computational Biology. 

Best regards,

Mohammad Sadegh Taghizadeh, Ph.D.

Academic Editor

PLOS Computational Biology

Shihua Zhang

Section Editor

PLOS Computational Biology

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Reviewer's Responses to Questions

Comments to the Authors:

Please note here if the review is uploaded as an attachment.

Reviewer #1: I am pleased with the authors’ careful and thorough responses to my previous comments. The revisions made to the manuscript have fully addressed the two minor issues I raised.

Regarding test coverage, the authors have now included the exact test coverage percentage (82%) in the ‘Availability’ section. This provides maximum transparency as requested and is a welcome addition.

Regarding stability issues, the authors have amended the ‘Limitations’ section to explicitly mention the stability issues encountered by some users during the usability study. This demonstrates a commendable level of transparency about the current state of the software and its areas for future improvement.

The authors have also taken care to address other editorial points, such as figure formatting. The manuscript is now significantly strengthened, clearly written, and presents a valuable open-source tool for the community. I have no further concern. The manuscript is now highly rigorous and scientifically sound which make it fit for publication in PLOS Computational Biology. The work is now ready to go further for the Editor-in-Chief’s final decision in line with the remaining peer reviewers’ comments.

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Have the authors made all data and (if applicable) computational code underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data and code 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 and code 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 or code —e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

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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:  Shafiu Adam Umar Shinge

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