Dear Dr. Maroilley,

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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PLOS One

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Additional Editor Comments:

Thank you for this contribution to PLOS One. All three reviewers agree that you describe an interesting and potentially useful CURE. As you note in the manuscript, this type of learning experience can be extremely valuable to our students. However, the reviewers also generally agreed that the manuscript should be revised. They express concerns about overstating the conclusions and the analysis of the data. I hope you find their comments useful as you contemplate revising this manuscript.

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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?

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Partly

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

Reviewer #1: No

Reviewer #2: N/A

Reviewer #3: No

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3. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: No

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Reviewer #1: In the manuscript titled “A Course-Undergraduate Research Experience (CURE) to explore the effect of structural variants on gene expression in C. elegans balancers,” Maroilley et al. describe the development and implementation of a CURE that focuses on the teaching of bioinformatics through an applied and inquiry-based approach. The authors developed a substantial number of materials to support the implementation of the CURE in the course MDSC 301. The course appears to be well thought-out and well-scaffolded to guide the students through the challenging material. Many undergraduate curriculums lack quality courses in bioinformatics; therefore, there is a clear value to this course and the approach the authors are taking to introduce this topic to their students.

Unfortunately, the assessment of the learning outcomes and value of the course to the students is very limited. Given that this manuscript was submitted as a research article, there does not appear to be enough robust analysis of the course to warrant it in this category. My recommendation would be for the authors to consider submitting the manuscript to an education journal, focusing on their pedagogical approach to the course.

Major Concerns:

• The actual assessment of the course is only described in a few sentences (lines 498-503) and is very limited in scope. The response rate of the survey was only 13% (9 students), which is unfortunately too low to obtain any substantial feedback. A higher response rate and a different experimental design would allow for more robust and informative assessment of the outcomes of the course for the students.

- These 9 students come from two separate cohorts. What was changed in the course from cohort 1 vs. cohort 2? Did this have an impact on the outcomes for the students?

- Did the impact of the course on the students vary by their major or educational background?

- Best practice would involve having both a pre-survey and post-survey, so that you can assess the growth of the students throughout the course. The authors only provided a post-assessment to evaluate the learning objectives and outcomes of the course. While the students were given an initial survey in the course and reflections throughout, these were not designed as assessment tools.

- Best practice would involve having the students complete the survey as part of the course (their participation in the research study would still be optional). This should result in a much higher response rate. Additionally, cohort 1 was assessed almost one year after they completed the course (course in winter 2023, assessment in winter 2024).

- Even better – Incorporate some of the reflection assignments into your assessment strategy (with approval from IRB and consent from the students).

- Although the course was implemented three times, only the outcomes of the first two cohorts were assessed.

- Based on the results shown in Figure 3, the only responses the students could provide were “strongly agree”, “somewhat agree”, or “neither agree or disagree”. Were students given the option to “somewhat disagree” and “strongly disagree”?

• The figures lack figure legends. They would benefit from stronger titles and detailed explanations.

• Figure 3A.

- As mentioned previously, did you allow students to “disagree” with the statements?

- The order of the statements in this figure seems random. It does not match the order of the questions in the survey, nor is it organized by the degree to which students agree with the statements or by topic.

- What do the numbers at the bottom represent (I assume number of students that responded?)

• Figure 3B.

- What do the numbers at the bottom represent? I assume % of students that somewhat or strongly agreed?

- Again, the order of these statements seems random.

Additional Comments:

• The manuscript would benefit from additional information on the background of the students that took this course. Was the course required for all students? Was it one of several elective courses? What prior lab experience did the students have prior to taking this course?

• You mentioned that you alter the course and Lab Book each semester, based on feedback from the students, instructor, and TAs (lines 188-190). What are some examples of how you have revised the Lab Book and course?

• The way some portions of this manuscript were written was a bit unusual. It felt like some of the sentences were truncated or missing words. I think it would benefit from additional editing.

• Lines 121-123: You describe that the course has been offered to three cohorts of students. However, you only provide survey results for two of these cohorts.

• Lines 412-422. Walking Gallery. This section is not clear. I am not sure what they are doing in this part of the course and its objective.

• Lines 440-442: What do you mean that the presentation of the posters is “not subject to any evaluation for the students’ participation”? How do you know that the students understand the project and their results, and that they are meeting the learning objectives of the course? Even at professional conferences, presenters are challenged with their thinking and asked questions about their project. Plus, how do students learn if they don’t receive feedback? The experience can be positive and encouraging and still provide constructive feedback so that the students can improve in the future.

• Lines 557-560. What is the evidence that you have created an inclusive learning environment in this course and that students are supported in their learning? While I am sure you aim for these objectives, you need to provide evidence to support this statement.

Reviewer #2: Overall, this is an excellent CURE and I believe that other educators will greatly benefit from following this example. With that being said, I do have a few comments regarding the overall structure and flow of the manuscript.

Remove the term "nowadays" found on lines 26 and 66. This is an unnecessary filler term.

In your introduction only very briefly defines what a CURE is and there is no decision on even the hallmarks of a CURE until lines 264-287 in your results section. These defined hallmarks should be discussed in the introduction. That way your reader knowns exactly how a CURE is defined by the literature.

Lines 263-496 (all found in the results section) should be moved out of the results section. This is the heart of your course design. If you are keeping with the traditional introduction, methods, results, discussion this this course design should be moved to the methods section with a subsection labeled as Course Design. These are not results but rather all of the important information on how the course was set up and executed.

Line 147-148 there is a survey mentioned. This is confusing because there has been no mention of this survey and it is not brought up again until the Survey and Ethics statement starting on line 196. To help with the flow the Survey and Ethics Statement subsection (line 196-207) should be moved and place before the CURE Implementation subsection (line 140-148).

The best approach at this point would be a reorganization of the paper in order to help with the flow and to make it seem less disjointed. It appears the overall focus is the design of the course so that should be made more clear in the introduction and the methods should be dedicated to the course design rather than the results section.

Reviewer #3: The paper addresses a genuinely important gap: the integration of authentic, original research into undergraduate bioinformatics education through a Course-based Undergraduate Research Experience (CURE). The course design is creative, well-scaffolded, and grounded in established CURE pedagogy. The commitment to open science via sharing the Lab Book, datasets, and protocols publicly is exemplary and adds considerable value for the broader community of bioinformatics educators.

However, the manuscript in its current form requires major revision before it can be accepted. The concerns are concentrated in three areas: (1) the educational outcome claims substantially overreach the data, which rests on a critically small and self-selected survey sample; (2) the scientific discovery component lacks the quantitative analysis necessary for publication as a research finding; and (3) the writing requires thorough language editing to address recurrent grammatical issues, sentence-level clarity, and narrative structure.

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what does this mean?). If published, this will include your full peer review and any attached files.

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

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Attachments

Attachment

Submitted filename: PONE-D-25-66689_ReviewerComments.pdf

A Course-Undergraduate Research Experience (CURE) to explore the effect of structural variants on gene expression in C. elegans balancers

PONE-D-25-66689R1

Dear Dr. Maroilley,

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,

David R Wessner, Ph.D.

Academic Editor

PLOS One

Additional Editor Comments (optional):

Thank you so much for submitting this revised mansucript. The reviewers agreed that you addressed their original concerns. As a result, I would like to accept this mansucript for publication. It will be a nice addition to the literature. One reviewer did note some minor issues (grammar, mostly) that shoud be addressed. I included them below. Please make these changes before before the work is published. Thanks again for submitting htis manuscript to PLOS One.

Reviwer comments:

1. The authors regularly switch between past and present tense. For example, lines 77-84, lines 288-296, and lines 331-339. Other small grammar and clarity issues are also present throughout the text. For example, lines 398-401 are not clear. Line 395, "the teaching time talked..."

2. All abbreviations/acronyms need to be defined. Line 95 (WGS) and line 114 (BHSc).

3. Line 115, you say that the CURE was implemented 4 times. Line 132-133, you say it was 3 times, but then list 4 semesters. Which is correct?

4. Line 131, you say the course has a 45-student capacity, but then in line 133, you say it accommodated up to 44 students each semester. I know what you are trying to say, but it ends up being a bit confusing with the way it is written.

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #1: (No Response)

Reviewer #2: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions??>

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

Reviewer #1: Yes

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: The revised manuscript is greatly improved from the first submission. However, a few minor issues should still be addressed:

1. While the grammar and writing quality is better, it still would benefit from additional improvement. In particular, the authors regularly switch between past and present tense. For example, lines 77-84, lines 288-296, and lines 331-339. Other small grammar and clarity issues are also present throughout the text. For example, lines 398-401 are not clear. Line 395, "the teaching time talked..."

2. All abbreviations/acronyms need to be defined. Line 95 (WGS) and line 114 (BHSc).

3. Line 115, you say that the CURE was implemented 4 times. Line 132-133, you say it was 3 times, but then list 4 semesters. Which is correct?

4. Line 131, you say the course has a 45-student capacity, but then in line 133, you say it accommodated up to 44 students each semester. I know what you are trying to say, but it ends up being a bit confusing with the way it is written.

5. Line 551. Switching from a description of the CURE and its results to the description of the chromosomal translocation is abrupt. It would benefit from a sentence or two transition.

Reviewer #2: (No Response)

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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: No

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