PONE-D-19-25581

Genes associated with body weight gain and feed intake identified by meta-analysis of the mesenteric fat from crossbred beef steers

PLOS ONE

Dear Dr. Lindholm-Perry,

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

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: 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: Dear Authors:

This MS finally made it clear to me that my approach to genomics in the early 2000 s with 5 animals per treatment group and single marker genes for lipogenesis, fat oxidation etc gave us little information. On the other hand this work also did not pinpoint too many DE genes one would think of from a biological-function perspective.

This was a big project and authors and ever new emerging bioinformatic tools allowed you to do extensive analyses and assessment. The overall assessments are interesting since there are other data sets point to CNS, immune function system/inflammation etc. Once again I see no DE for genes involved in protein turnover and of course protein synthesis is under transnational control. There are also many other factors that effect gene expression qualitatively and quantitatively. Such would include epi-genetic effects, nucleosomes and nucleic acid post transcriptional remodeling, mi RNA, long non-coding RNA etc.

I like the way the paper is written, but it may be a bit wordy and all those gene abbreviations do not make for pleasant reading (there appear to be no alternatives either).

I have a few comments/queries:

Line 54 High fat diets various various biological reasons in ruminants seldom exceed 5% fat and in comparison to chickens and pigs such diet could easily contain 20% fat while in humans in the US many consume a 50% plus fat calorie diet. So this high fat is only applicable to ruminants.

Line 112 says: Length of time between the feeding trial end and slaughter were 12-18 etc dates. Gene expression can be pretty sensitive to type and amount of feed. Once the trial was ended, were the animals continued on the same diet and at the same intake level until tissue sampling? Was feed efficiency maintained post feeding trial until slaughter. Would a time course sampling strategy at intervals throughout the feeding trail result more representative data. Often when a trial is over and all animals are to the same finish and weight there are no more differences. That is a problem of sampling only at the end of the trial.

Much of the phenotypic expression that is observed also depends on regulation of enzyme catalysis by covalent modifications and allosteric factors.

Reviewer #2: Manuscript PONE-D-19-25581 aimed to identify genes that may be differentially expressed in steers with high and low BW gain and feed intake. The study is technically and scientifically sound but authors need to improve the main messages that can be taken from their nice research scope.

Line 52 any idea on how much a farmer can save? Please give an estimate in %

Line 53 what is usable? Please elaborate

Lines 68-75 please describe your study hypothesis. It seems that it is somehow encrypted in this paragraph, could you please be more precise on your research expectations

Line 89 is it 64 to 92 days. Is that the sampling period? Please clarify

Lines 88-94 please provide forage to concentrate ratio and the rationale behind the diet formulation i.e., NRC… here and later for the other diet descriptions

Line 91 after steakmater add (protein supplement; Land..

Line 122 add city and country and also catalogue number here and anywhere appropriate

Line 278 how can you overcome the fact that you have 5 cohort animals – does that influence or not your results? Please elaborate

Lines 417 to 425 what would be the take-home message? Please try to deliver more precise. You have 5 cohorts of animals, each of them with precise feeding managements can you relate those variables with your transcriptomic results and BW gain and feed intake. The main issue perhaps is that in its present version your conclusion statements have not been landed in a way that the answered your initial objectives.

Reviewer #3: This is a very well-written manuscript describing a meta-analysis of RNAseq in mesenteric fat tissue in regards to body weight gain and feed efficiency. While I agree with the choice of using an adjusted p-value of 0.01, I would appreciate an acknowledgement of the false positive errors that the lack of concordance between cohorts can be due to genes being identified as DE by chance.

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

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Genes associated with body weight gain and feed intake identified by meta-analysis of the mesenteric fat from crossbred beef steers

PONE-D-19-25581R1

Dear Dr. Lindholm-Perry,

We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.

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With kind regards,

Juan J Loor

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

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: All comments have been addressed

Reviewer #3: All comments have been addressed

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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

Reviewer #3: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: 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

Reviewer #2: Yes

Reviewer #3: 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

Reviewer #2: Yes

Reviewer #3: 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: Very good job of revision.

Line 166... developed in (5) was used; give a name of the authors

Line 290 This allowed us to identify a several genes; remove the "a"

Reviewer #2: authors have made all suggested corrections

Reviewer #3: (No Response)

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No