PONE-D-24-23787SCRMshaw: Supervised cis-regulatory module prediction for insect genomesPLOS ONE

Dear Dr. Halfon,

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.

Add a little more into the opening paragraph, about the problem of predicting regulatory elements. And specifically, which other tools attempt the same as SCRMshaw? Mention a few benefits/drawbacks of SCRMshaw vs these tools, and cite a/some benchmarking papers on that.

Minor point

Line 108

Is this the best heading for this section? “Expected Results”

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Arnar Palsson, Ph.D.

Academic Editor

PLOS ONE

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Additional Editor Comments:

This is a fine manuscript. Sorry for the delay, we were waiting on reviewer 2 that, eventually didnt come through.

Add a little more into the opening paragraph, about the problem of predicting regulatory elements. And specifically, which other tools attempt the same as SCRMshaw? Mention a few benefits/drawbacks of SCRMshaw vs these tools, and cite a/some benchmarking papers on that.

Minor point

Line 108

Is this the best heading for this section? “Expected Results”

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript report a protocol which is of utility to the research community and adds value to the published literature?

Reviewer #1: Yes

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2. Has the protocol been described in sufficient detail?

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The step-by-step protocol should contain sufficient detail for another researcher to be able to reproduce all experiments and analyses.

Reviewer #1: Yes

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3. Does the protocol describe a validated method?

The manuscript must demonstrate that the protocol achieves its intended purpose: either by containing appropriate validation data, or referencing at least one original research article in which the protocol was used to generate data.

Reviewer #1: Yes

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Reviewer #1: N/A

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5. Is the article presented in an intelligible fashion and written in standard English?

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Reviewer #1: Yes

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6. Review Comments to the Author

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Reviewer #1: 1. The manuscript describes an updated protocol of SCRMshaw, a computational tool designed to predict cis-regulatory modules in insect genomes. This updated version is of significant utility to the research community for several reasons. First, its minimal resource requirements make it accessible to a wide range of researchers, including those with limited computational skills and resources. Second, the flexibility of SCRMshaw to be tailored for specific needs adds considerable value to the tool. This update which includes a detailed pipeline, available via GitHub and the provision of a living protocol linked to the article further enhance its utility and relevance, ensuring that it can be easily adapted and updated by the research community.

2. The protocol provided in the Materials and Methods section of the manuscript and in protocols.io shows that the authors have meticulously detailed the steps involved in using SCRMshaw. The protocol covers all the necessary stages, from the initial preparation of the genome sequence to the final annotation of regulatory elements. Each step is accompanied by clear instructions and helpful screenshots, and the inclusion of scripts available via GitHub ensures that the users can easily implement the protocol. A great advantage of this detailed protocol, is the notes and recommendations for users with basic or optimal computational resources. Therefore, the protocol has been described in sufficient detail to allow their implementation by the research community.

3. The SCRMshaw protocol describes a validated method that has been tested in Halfon's lab and supported by scientific evidence developed since 2009. This foundation has triggered updated and effective versions of the protocol. The use of training data from well-characterized Drosophila regulatory sequences, and their application in the annotation of 33 insect regulatory genomes, demonstrate its robustness and reliability across multiples datasets and species. Notably, the genome annotation of the most relevant Orders in the Insecta class, such as Hemiptera, Hymenoptera, Coleoptera, Lepidoptera and Diptera, makes this tool a useful reference for searching cis-regulatory sequences in both model and non-model organisms currently studied by the research community. The detailed description of the end-to-end pipeline, from genome sequencing to regulatory annotation, further supports the validity of the method.

4. The manuscript is well-written in standard English. In general, the language used is precise and appropriate for a scientific audience, clearly describing the purpose and advantages of the SCRMshaw tool and presenting a logical and coherent flow of information.

Suggestions for improvement:

-The authors should include a brief discussion on the limitations of the SCRMshaw tool and how these might be addressed in future versions and updates. This would provide a balanced view and help researchers understand the tool's scope.

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Reviewer #1: Yes: Keity J. Farfán-Pira

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SCRMshaw: Supervised cis-regulatory module prediction for insect genomes

PONE-D-24-23787R1

Dear Dr. Halfon,

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.

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Kind regards,

Arnar Palsson, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: