On 2014 Aug 06, Samir Ounzain commented:

Thank you Dr Matkovich for clarifying these points, both myself and readers will appreciate this quick and comprehensive response. I understand that the review process can lead to absence of specific pieces of literature, especially those published in a comparable time frame. However typically in the process of revision it is important to cite even recently pubished work and discuss if highly relevant to your study. Many pieces of work are submitted months if not years before final acceptance but we all have a responsibility to correctly cite and discuss highly relevant recent work during any revisions. I would also like to clarify that citations 4 and 26 by the Hermann group and ourselves are not the most relevant in this context. Citation 24 is a review article and reference 4 describes Fendrr and not the recent more global characterisation of embryonic cardiac lncRNAs by the Herrmann group (for benefit of community these citations are in original post). For the benefit of everybody in this exciting new and emerging field it is of importance that all relevant and recent studies are included and discussed. Hopefully our discussion here as raised these points to the benefit of the field. I congratulate you on your important piece work, and especially your delineation of putative –cis control of proximal coding genes via lncRNAs characterised in your study. I think –cis control, especially for those lncRNAs templated by cardiac enhancers will emerge as an important regulatory function for the global enhancer reprogramming that underpins the re-activation of the fetal gene program and subsequent pathological remodelling. Your work provides further signficant evidence for the potential importance of lncRNAs in the developing and remodelling heart. I look forward to further studies from your Laboratory and the community. Functional and phenotypic characterisation of these exciting new cardiac enriched molecules is now of importance for all in the community.

On 2014 Aug 05, Scot Matkovich commented:

I'm pleased that our recent publication has already attracted interested readers. With regard to the references we cited and the publication date of other literature in the field, we first submitted this paper to PNAS in November 2013; as is the trend at a lot of journals, the 'submission date' on the final paper is actually the receipt date of the most recent major revision (June 2014). We had already cited papers from the Herrmann and Pedrazzini groups as references 4 and 26. I would suggest that neither the peer review process nor the authors have been delinquent in failing to cite extremely recent literature, whose e-publication dates were largely coincident with the preparation of our revised manuscript.

I would like to clarify one misrepresentation of our study made by Dr Ounzain. We did not attempt to identify 'novel' murine lncRNAs in the developing and adult heart, but rather sought to bring a degree of curation and refinement to the characterization of cardiac lncRNAs by focusing on a limited set of lncRNAs with strong evidence for existence as separate entities. We tried to avoid including database entries which may be spuriously annotated fragments of other RNAs, as indicated in our Supplemental Methods. Using this carefully selected set of lncRNAs, we evaluated the extent to which they were regulated during growth of the embryonic heart or pressure overload-induced hypertrophy. I feel it is likely that a similar disparity of lncRNA regulation between these two growth states will be found no matter how many lncRNAs are included in such a comparison.

Nonetheless, I would like to thank Dr Ounzain for pointing out that his recent study provides a thorough catalog of 'known' and 'novel' murine cardiac lncRNAs as determined by ab initio reconstruction of paired-end RNAseq transcripts. As annotation improves with time and a common nomenclature for lncRNAs is decided, both of our raw sequencing read datasets should prove fruitful for others to mine and to investigate cardiac lncRNA regulation. The mechanistic studies we performed on reciprocally regulated lncRNAs and adjacent coding mRNAs should provide a useful framework for evaluating the extent to which other lncRNAs may regulate local transcription.

On 2014 Aug 04, Samir Ounzain commented:

Overall a nice piece of work further extending the characterisation and identification of novel murine lncRNAs within the developing and adult heart post injury. However, sadly, a number of important publications predating the submission date of this manuscript were omitted.Specifically within introduction authors state ''Indeed, it is not yet known with certainty which lncRNAs are expressed in mouse hearts, nor have the identities of lncRNAs exhibiting 'cardiac-enriched' expression been defined''.

These points have been addressed in previous publications and I kindly refer the authors of this manuscript and readers here on PubMed to the following important publications which were published prior to this paper being submitted. Sadly the peer review process also missed these

1: Werber M, Wittler L, Timmermann B, Grote P, Herrmann BG. The tissue-specific transcriptomic landscape of the mid-gestational mouse embryo. Development. 2014 Jun;141(11):2325-30. doi: 10.1242/dev.105858. Epub 2014 May 6. PubMed PMID: 24803591.

1: Ounzain S, Micheletti R, Beckmann T, Schroen B, Alexanian M, Pezzuto I, Crippa S, Nemir M, Sarre A, Johnson R, Dauvillier J, Burdet F, Ibberson M, Guigó R, Xenarios I, Heymans S, Pedrazzini T. Genome-wide profiling of the cardiac transcriptome after myocardial infarction identifies novel heart-specific long non-coding RNAs. Eur Heart J. 2014 Apr 30. [Epub ahead of print] PubMed PMID: 24786300.

On 2014 Aug 04, Samir Ounzain commented:

Overall a nice piece of work further extending the characterisation and identification of novel murine lncRNAs within the developing and adult heart post injury. However, sadly, a number of important publications predating the submission date of this manuscript were omitted.Specifically within introduction authors state ''Indeed, it is not yet known with certainty which lncRNAs are expressed in mouse hearts, nor have the identities of lncRNAs exhibiting 'cardiac-enriched' expression been defined''.

These points have been addressed in previous publications and I kindly refer the authors of this manuscript and readers here on PubMed to the following important publications which were published prior to this paper being submitted. Sadly the peer review process also missed these

1: Werber M, Wittler L, Timmermann B, Grote P, Herrmann BG. The tissue-specific transcriptomic landscape of the mid-gestational mouse embryo. Development. 2014 Jun;141(11):2325-30. doi: 10.1242/dev.105858. Epub 2014 May 6. PubMed PMID: 24803591.

1: Ounzain S, Micheletti R, Beckmann T, Schroen B, Alexanian M, Pezzuto I, Crippa S, Nemir M, Sarre A, Johnson R, Dauvillier J, Burdet F, Ibberson M, Guigó R, Xenarios I, Heymans S, Pedrazzini T. Genome-wide profiling of the cardiac transcriptome after myocardial infarction identifies novel heart-specific long non-coding RNAs. Eur Heart J. 2014 Apr 30. [Epub ahead of print] PubMed PMID: 24786300.

On 2014 Aug 05, Scot Matkovich commented:

I'm pleased that our recent publication has already attracted interested readers. With regard to the references we cited and the publication date of other literature in the field, we first submitted this paper to PNAS in November 2013; as is the trend at a lot of journals, the 'submission date' on the final paper is actually the receipt date of the most recent major revision (June 2014). We had already cited papers from the Herrmann and Pedrazzini groups as references 4 and 26. I would suggest that neither the peer review process nor the authors have been delinquent in failing to cite extremely recent literature, whose e-publication dates were largely coincident with the preparation of our revised manuscript.

I would like to clarify one misrepresentation of our study made by Dr Ounzain. We did not attempt to identify 'novel' murine lncRNAs in the developing and adult heart, but rather sought to bring a degree of curation and refinement to the characterization of cardiac lncRNAs by focusing on a limited set of lncRNAs with strong evidence for existence as separate entities. We tried to avoid including database entries which may be spuriously annotated fragments of other RNAs, as indicated in our Supplemental Methods. Using this carefully selected set of lncRNAs, we evaluated the extent to which they were regulated during growth of the embryonic heart or pressure overload-induced hypertrophy. I feel it is likely that a similar disparity of lncRNA regulation between these two growth states will be found no matter how many lncRNAs are included in such a comparison.

Nonetheless, I would like to thank Dr Ounzain for pointing out that his recent study provides a thorough catalog of 'known' and 'novel' murine cardiac lncRNAs as determined by ab initio reconstruction of paired-end RNAseq transcripts. As annotation improves with time and a common nomenclature for lncRNAs is decided, both of our raw sequencing read datasets should prove fruitful for others to mine and to investigate cardiac lncRNA regulation. The mechanistic studies we performed on reciprocally regulated lncRNAs and adjacent coding mRNAs should provide a useful framework for evaluating the extent to which other lncRNAs may regulate local transcription.

On 2014 Aug 06, Samir Ounzain commented:

Thank you Dr Matkovich for clarifying these points, both myself and readers will appreciate this quick and comprehensive response. I understand that the review process can lead to absence of specific pieces of literature, especially those published in a comparable time frame. However typically in the process of revision it is important to cite even recently pubished work and discuss if highly relevant to your study. Many pieces of work are submitted months if not years before final acceptance but we all have a responsibility to correctly cite and discuss highly relevant recent work during any revisions. I would also like to clarify that citations 4 and 26 by the Hermann group and ourselves are not the most relevant in this context. Citation 24 is a review article and reference 4 describes Fendrr and not the recent more global characterisation of embryonic cardiac lncRNAs by the Herrmann group (for benefit of community these citations are in original post). For the benefit of everybody in this exciting new and emerging field it is of importance that all relevant and recent studies are included and discussed. Hopefully our discussion here as raised these points to the benefit of the field. I congratulate you on your important piece work, and especially your delineation of putative –cis control of proximal coding genes via lncRNAs characterised in your study. I think –cis control, especially for those lncRNAs templated by cardiac enhancers will emerge as an important regulatory function for the global enhancer reprogramming that underpins the re-activation of the fetal gene program and subsequent pathological remodelling. Your work provides further signficant evidence for the potential importance of lncRNAs in the developing and remodelling heart. I look forward to further studies from your Laboratory and the community. Functional and phenotypic characterisation of these exciting new cardiac enriched molecules is now of importance for all in the community.