miRNA Regulatory Functions in Farm Animal Diseases, and Biomarker Potentials for Effective Therapies
, Pier-Luc Dudemaine 1, Manisha Mathur 3, Prashanth Suravajhala 4, Xin Zhao 5 and Eveline M. Ibeagha-Awemu 1,*Round 1
Reviewer 1 Report
In an extensive manuscript presented for review, the authors describe changes in miRNA expression in various diseases of farm animals. They also indicate the possibility of these miRNAs occurring as biomarkers.
Unfortunately, this manuscript is overloaded and therefore difficult to read for the recipient, despite the exhaustive amount of information. Therefore, it should be rewritten.
The most interesting - chapter three - has been hidden behind the overwhelming amount of information concerning miRNAs expression changes in various diseases of different farm animals species, so it is difficult to reach it at all. It should appear immediately after the introduction and determine the manuscript plan. The authors present potential applications of miRNAs for biomarkers in Fig1C, which is crucial for this review and what is reflected in the manuscript title. Therefore, subdivided into individual functions of miRNAs, instead into species and diseases respectively, they should present the information from chapter 2.
In addition to these remarks, the authors should pay attention to the table layout, as it is illegible in its current form. Leaving a space between the lines, would allow easier reading the information.
Author Response
Reviewer #1
In an extensive manuscript presented for review, the authors describe changes in miRNA expression in various diseases of farm animals. They also indicate the possibility of these miRNAs occurring as biomarkers.
Response: Thank for your comments
Unfortunately, this manuscript is overloaded and therefore difficult to read for the recipient, despite the exhaustive amount of information. Therefore, it should be rewritten.
Response: We have re-organized the manuscript according to your suggestions. Less relevant portions of text and references have been removed and material synthesized for fluidity.Than you again for your valuable comments
The most interesting - chapter three - has been hidden behind the overwhelming amount of information concerning miRNAs expression changes in various diseases of different farm animals species, so it is difficult to reach it at all. It should appear immediately after the introduction and determine the manuscript plan. The authors present potential applications of miRNAs for biomarkers in Fig1C, which is crucial for this review and what is reflected in the manuscript title.
Response: We moved section 3 (now section 2) below the introduction and also expanded the section.Thank you
Therefore, subdivided into individual functions of miRNAs, instead into species and diseases respectively, they should present the information from chapter 2.
Response: Since each disease is governed by specific mechanisms, we prefer to keep the information according to species separately. Moreover, there are too many miRNAs so trying to centre the review around the changed miRNAs will be laborious to write and to read. We have removed redundant text and also highlighted some miRNAs which are associated to two or more diseases (see section 3.5).
In addition to these remarks, the authors should pay attention to the table layout, as it is illegible in its current form. Leaving a space between the lines, would allow easier reading the information.
Response: Thank you for your recommendation. We followed journal guidelines in creating the tables. They have been formatted as per your recommendations.
Reviewer 2 Report
I am grateful for the opportunity to review the manuscript titled “MiRNA regulatory functions in farm animal diseases, and biomarker potentials for effective therapies”. In this manuscript the authors extensively review several studies evaluating involvement of miRNAs in disease development and the body’s endeavours to fight or overcome different infections or diseases in livestock species. Additionally, the authors give insightful proposal about the future of using miRNAs as biomarkers or therapeutic tools different diseases in livestock species. This is a good manuscript that will benefit researcher and the livestock industry; however, I have a few comments and suggestion that the authors could consider to improve their manuscript.
Apart from mentioning the studies and the results one by one it would also be interesting to see, which miRNAs have been reported to be involved in the same disease across different studies or involved in different diseases across different studies. Seems like each study has reported unique results or observation, nothing common between studies? That should be explored. The studies in each paragraph or subsection of the review should integrated rather more than the current status of the manuscript.
Addition of transition phrases as the authors transit from one study to another (in the larger part of the manuscript’s body) could greatly improve the story, currently each study being discussed or reviewed seem to give an independent picture. This also applies to your sentences, though each sentence should present new information to the reader, the sentences should show connection to each other. In many instances each sentence is started as if it is presenting completely new information from the preceding sentence, when in actual sense it is just a continuation of the facts presented in the previous sentence. There should be smooth transition from one sentence to another.
Line32: What do you mean by “activities”? Could try to find a fitting phrase.
Line33-34: How does “MiR-33 NAs often have multiple transcription start sites” relate to the rest of the sentence?
Line43: Remove “etc”.
Line52-54: Why don’t you give some of the experimental wet or wet lab approaches as done elsewhere.
Line119: Add “which are” before “involved”.
Line190: Add “prediction” before “model”.
Line193: Change “node” to “nodes”.
Line194: Replace “host” with “host’s immune cells” before interaction.
Line210-211: Need a citation for this information.
Line331-332: Need citation for this information.
Line414: What do you mean by “y the method”? Probably you wanted to write “Using the method”.
Line417: This does not seem to be a normal citation (Lian et al…), please check and correct.
Line431: I think “…..target genes of DE miRNA” should be “……..target genes of the DE miRNAs”, please revise.
Line442-444: Please check punctuation of this sentence, seems to have commas where they are not needed.
Line444-448: The second part of this sentence is not clear. Please consider dividing the sentence into two. “ likely via targeting and repressing yes-associated protein (YAP1), cyclin E (CCNE1) and Drosophila inhibitor of apoptosis protein 1 (DIAP1) genes 447 [123].” should be a different sentence.
Line434-466: Lots of studies’ results are presented, but what is the overall picture from all these studies, a sentence or two mentioning what is found interesting across studies would be more interesting.
I think it would be great to consider adding a short paragraph on Equine as well.
Line586: What do you mean by “miRNAs” impact animal health.
Line635: How would biomarkers for breeding be like? Since selection and breeding are complex processes usually involving multiple traits, do you think identifying SNP markers located in stably differentially expressed miRNAs to enrich already available SNP or marker panels would be interesting or beneficial to the livestock production industry?
Line670-671: Do you think it is really that crucial to understand the role of the molecule in disease pathogenesis before being adopted as a biomarker as you have said here “Before adopting miRNAs as biomarkers, it is crucial to understand their roles in disease pathogenesis.”?
Line703: I think it would be expensive to develop miRNA-based therapeutics than developing miRNA biomarkers.
Author Response
Reviewer #2
I am grateful for the opportunity to review the manuscript titled “MiRNA regulatory functions in farm animal diseases, and biomarker potentials for effective therapies”. In this manuscript the authors extensively review several studies evaluating involvement of miRNAs in disease development and the body’s endeavours to fight or overcome different infections or diseases in livestock species. Additionally, the authors give insightful proposal about the future of using miRNAs as biomarkers or therapeutic tools different diseases in livestock species. This is a good manuscript that will benefit researcher and the livestock industry; however, I have a few comments and suggestion that the authors could consider to improve their manuscript.
Apart from mentioning the studies and the results one by one it would also be interesting to see, which miRNAs have been reported to be involved in the same disease across different studies or involved in different diseases across different studies. Seems like each study has reported unique results or observation, nothing common between studies? That should be explored. The studies in each paragraph or subsection of the review should integrated rather more than the current status of the manuscript.
Addition of transition phrases as the authors transit from one study to another (in the larger part of the manuscript’s body) could greatly improve the story, currently each study being discussed or reviewed seem to give an independent picture. This also applies to your sentences, though each sentence should present new information to the reader, the sentences should show connection to each other. In many instances each sentence is started as if it is presenting completely new information from the preceding sentence, when in actual sense it is just a continuation of the facts presented in the previous sentence. There should be smooth transition from one sentence to another.
Line32: What do you mean by “activities”? Could try to find a fitting phrase.
Response: We change it to ‘expression’. See line 33.
Line33-34: How does “MiR-33 NAs often have multiple transcription start sites” relate to the rest of the sentence?
Response: We removed this portion of the text.
Line43: Remove “etc”.
Response: We removed ‘etc’. See line 43.
Line52-54: Why don’t you give some of the experimental wet or wet lab approaches as done elsewhere.
Response: We summarized them in subsequent sections.
Line119: Add “which are” before “involved”.
Response: Added, thank you. The whole section has been re-organized.
Line190: Add “prediction” before “model”.
Response: Done. The whole section has been re-organized.
Line193: Change “node” to “nodes”.
Response: Done
Line194: Replace “host” with “host’s immune cells” before interaction.
Response: Done. The whole section has been re-organized.
Line210-211: Need a citation for this information.
Response: Done. The whole section has been re-organized.
Line 331-332: Need citation for this information.
Response: Done. The whole section has been re-organized.
Line414: What do you mean by “y the method”? Probably you wanted to write “Using the method”.
Response. Corrected
Line417: This does not seem to be a normal citation (Lian et al…), please check and correct.
Response: We corrected (Lian et al [115] )
Line431: I think “…..target genes of DE miRNA” should be “……..target genes of the DE miRNAs”, please revise.
Response: Corrected, thank you. The whole section has been re-organized.
Line442-444: Please check punctuation of this sentence, seems to have commas where they are not needed.
Response: We corrected it
Line444-448: The second part of this sentence is not clear. Please consider dividing the sentence into two. “ likely via targeting and repressing yes-associated protein (YAP1), cyclin E (CCNE1) and Drosophila inhibitor of apoptosis protein 1 (DIAP1) genes 447 [123].” should be a different sentence.
Response: Statement revised for clarity. See lines472-475
Line434-466: Lots of studies’ results are presented, but what is the overall picture from all these studies, a sentence or two mentioning what is found interesting across studies would be more interesting.
Response: We added section 3.5 to address this.
I think it would be great to consider adding a short paragraph on Equine as well.
Response: The manuscript is already too long so we prefer not add Equine.
Line586: What do you mean by “miRNAs” impact animal health.
Response: We changed to ‘relate’
Line635: How would biomarkers for breeding be like? Since selection and breeding are complex processes usually involving multiple traits, do you think identifying SNP markers located in stably differentially expressed miRNAs to enrich already available SNP or marker panels would be interesting or beneficial to the livestock production industry?
Response: Thank you for the insightful comment. The miRNA markers could directly indicate the status of disease. In addition, a group of miRNAs can be used to score diseases. In addition, as the reviewer mentioned, we can also use the SNPs in miRNA genes for breeding purpose
Line670-671: Do you think it is really that crucial to understand the role of the molecule in disease pathogenesis before being adopted as a biomarker as you have said here “Before adopting miRNAs as biomarkers, it is crucial to understand their roles in disease pathogenesis.”?
Response: Not necessarily. However, understanding the role of a miRNA in disease pathogenesis can further its usefulness. For example, we can combine both the information on miRNA function and their target genes for better prediction of diseases outcome or development of therapeutic approaches.
Line703: I think it would be expensive to develop miRNA-based therapeutics than developing miRNA biomarkers.
Response: We completely agree with the reviewer. However, it is possible to develop both miRNA biomarkers and miRNA therapeutics. The circumstance and the cost will be weighed against the benefits and the correct application will be developed for livestock management.
Reviewer 3 Report
This work is very wide, including many livestock species. Unfortunately, some species are not present such as Equus caballus and Oryctolagus cuniculus. For this reason I suggest to change “farm animal” with “some/selected farm animal” and “livestock” with “some/selected livestock species” or similar words where it is necessary to indicate that only some species are considered.
Line 142: “were significantly DE post-infection” these miRNAs are up- or down-regulated? Please describe with more details.
A summary of the listed researches and findings is lacking in any section. Please add. The synthesis is very important if one of the aim of the authors is to suggest potential biomarkers. Furthermore, a comparison of the results obtained in different species for similar diseases (i.e. viral diseases, etc.)
Line 80: 2.MIRNA … > 2. MiRNA …
Line 327-328: please correct
Author Response
Reviewer #3
This work is very wide, including many livestock species. Unfortunately, some species are not present such as Equus caballus and Oryctolagus cuniculus. For this reason I suggest to change “farm animal” with “some/selected farm animal” and “livestock” with “some/selected livestock species” or similar words where it is necessary to indicate that only some species are considered.
Response: The manuscript is already too long so we prefer not to add Equus caballus and Oryctolagus cuniculus. We retained the term ‘farm animal’ as we already specified in the relevant sections the specific farm animals under study.
Line 142: “were significantly DE post-infection” these miRNAs are up- or down-regulated? Please describe with more details.
Response: corrected
A summary of the listed researches and findings is lacking in any section. Please add. The synthesis is very important if one of the aim of the authors is to suggest potential biomarkers. Furthermore, a comparison of the results obtained in different species for similar diseases (i.e. viral diseases, etc.)
Response: We added summaries for each section
Line 80: 2.MIRNA … > 2. MiRNA …
Response: Corrected.
Line 327-328: please correct
Response: Corrected
