PONE-D-23-00875Transposable element insertions in 1000 Swedish individualsPLOS ONE

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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: Partly

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

Reviewer #1: Yes

Reviewer #2: No

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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: The manuscript is focused on the transposable elements insertion events in 1000 swedish population. 66% of TE

insertions in SweGen were present at >1% in the 1KGP databases. Although ~0.7% of those insertions affect protein coding genes, they rarely affect known disease casing genes (<0.1%). Those data are clear and enough to publish to PLOS ONE.

Reviewer #2: Review

The manuscript was aimed to analyze transposable element insertions in 1000 Swedish individuals and they create a population specific TE insertion data base. They also tried to evaluate the TE insertion workflow on two clinical cases where pathogenic TE insertion were suspected. There are some interesting findings presented, however I believe the manuscript is not currently of sufficient quality to be considered suitable for publication. I have set out my reservations below.

Major Concerns:

I find that the analyzes are unreliable because we cannot rely on references to have insertions without resorting to statistical tests. It is better to use the Kmeans method. Furthermore, the RetroSeq tool used in this study is not specific to insertion and is based on orthology. Furthermore, given that the authors analyzed short reads, it is therefore essential to verify the insertions found by PCR or to validate them using another tool.

Minor Concerns :

1/ Keywords: mobile elements are synonym to transposable elements.

Keep one of the two keywords.

2/ Introduction :

Line 42-43: “The reasons for this could be due to the specific disease-causing gene not being described or that the underlying cause is not (mono)genetic”. It could also be due to epigenetic factors.

Line 55: The sentence « TE are DNA sequences that compose around 50% of the human genome [6].TE are DNA sequences that can change their position in the genome should be reformulated.” Should be replaced by« TE are DNA sequences that compose around 50% of the human genome that can change their position in the genome [6].”

Line 56-58: authors have to precise that class II elements transpose via DNA with cut paste mechanism (which may explain the 2% proportion) whereas class I transpose with copy paste mechanism.

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Reviewer #1: No

Reviewer #2: No

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Attachments

Attachment

Submitted filename: Review PONE D 23 00875.docx

Transposable element insertions in 1000 Swedish individuals

PONE-D-23-00875R1

Dear Dr. Eisfeldt,

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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Kind regards,

Ruslan Kalendar

Academic Editor

PLOS ONE

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: (No Response)

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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

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

Reviewer #1: Yes

Reviewer #2: N/A

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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

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6. Review Comments to the Author

Reviewer #1: The manuscript of Transposable element insertions in 1000 Swedish individuals is important issue in relation to non-coding sequences. Authors are well revised it. Now, it is proper to publish to PLOS ONE.

Reviewer #2: Comments to the Author

The authors have addressed all of my areas of concern from their previous revision.

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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: No

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