<xhtml:span xmlns:xhtml="http://www.w3.org/1999/xhtml" xml:lang="en">A comparative genomic and phylogenomic study of Nocardia seriolae strains unveils high genetic homogeneity and open nature of the pangenome </xhtml:span>
This article has been Reviewed by the following groups
Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
The pathogen Nocardia seriolae is responsible for causing chronic granulomatous disease, known as fish nocardiosis, which has been observed in more than 40 species of fish cultured in marine and freshwater environments. Therefore, it is imperative to perform research to address and eradicate this substantial threat to the aquaculture industry. However, quantifying the negative impacts associated with this species is difficult because of insufficient data and underreporting. While several genomes are available in online databases, there is still a lack of comparative genomic analyses and studies on effective treatments, which is particularly important for aquaculture. To gain a deeper understanding of the pathogenic mechanisms associated with various Nocardia strains causing disease outbreaks and their virulence components, as well as the functional enrichment and genetic diversity during infection, it is crucial to develop a dependable and replicable pangenomic dataset. This study quantified Nocardia pangenome openness and discovered the biological processes that drive it. The study also found a substantial association between pangenome openness and numerous parameters such as genomic plasticity, gene synteny, single-copy phylogenomics, and pangenome prediction. The results showed genetic similarity across strains, indicating that the pangenome of this species is moving toward completeness. The diversity was supported by the similarity analysis, which revealed a high percentage of genes in the core genome and close association among the strains. Our findings provide valuable information and emphasize the necessity of sequencing novel genomes of N. serioale isolates to gain a deeper understanding of their diversity and patterns of adaptability.
Article activity feed
-
The reviewers have highlighted major concerns with the work presented. Please ensure that you address their comments.
-
Comments to Author
The manuscript presents a genomic exploration on a pathogen which is of importance in the fish industry. Thus, the analysis performed by the authors is of importance and is of interest in the industry. However, certain points should be addressed to solidify the presented work. Title: The title introduces the reader to concepts such as homogeneity and pangenomics. However, homogeneity is only addressed here and it is not discussed further in the manuscript. It would be suggested to address the use and meaning of "homogeneity" for the objectives addressed in the manuscript. It is understandable that the manuscript compares genomes and finds that these genomes do not present much variation. However, "homogeneity" might not be the correct word to address these differences and variation between genomes.
Comments to Author
The manuscript presents a genomic exploration on a pathogen which is of importance in the fish industry. Thus, the analysis performed by the authors is of importance and is of interest in the industry. However, certain points should be addressed to solidify the presented work. Title: The title introduces the reader to concepts such as homogeneity and pangenomics. However, homogeneity is only addressed here and it is not discussed further in the manuscript. It would be suggested to address the use and meaning of "homogeneity" for the objectives addressed in the manuscript. It is understandable that the manuscript compares genomes and finds that these genomes do not present much variation. However, "homogeneity" might not be the correct word to address these differences and variation between genomes. Introduction: The first paragraph does a good job describing the problematics around this pathogen. However, the manuscript would benefit itself if this is shortened, so as to keep the overall discussion focused on the genomics of N. seriolae. The important points here would be the economic problems that N. seriolae represents, and a brief introduction on the pathogenic process, so as to address virulence factors. Objective: The objective, as being addressed from the 80th line, can be read as ambitious. Genomics at this stage is mostly an exploratory tool, and it helps to define an objective for further studies. In this case, even if the findings of the study do contribute to knowledge for further studies in the species diversity, for example, it doesn't necessarily solve completely this question because of the limitation on information. It would be suggested to simplify the general aim of the work, reducing its scope taking into account the limits of genomic analysis. Materials and Methods: It is necessary to raise a concern regarding the use of 7 genomes in the overall pangenomic analysis. It is understood that for the objectives of the further analysis, like pathogenic islands, complete genomes are necessary. However, when it comes to the construction of the pangenome of a species, all genomic data from said species should be used, since completeness is not an issue in pangenomic analysis. It would be suggested to use complete and draft genomes of N. seriolae only for the pangenomic analysis. And for further analysis regarding the identification of genomic islands in the genomes, it would be advised to continue only with the 7 complete genomes. As a side note, at line 109, the authors should specify the version of IslandViewer used for the analysis. Results: Certain issues with the figures showing the results should be addressed: Supplementary Figure 3 would be more comprehensible if it uses the strain names rather than the GenBank Accession Numbers. Supplementary Figure 4 needs to have a more extensive description since it is not properly described and it is difficult to understand it as it is. Figures 3 and 4 would benefit from having bigger labels. Regarding Figure 4, a better description would be helpful for readers not familiar with pangenomics analysis. Regarding Figure 4, it is understood that the phylogenomic tree building described in methods is used here. However, the Supplementary Figure 3 also provides a tree using Neighbor-Joining. It would be better if the method of this tree is addressed too. It would also be suggested to have a bigger phylogenetic tree in the principal figures being shown. Discussion: A previous work with 2 sub-clades is addressed. It would be interesting to get the details on how both works differ and might be of use to understand the benefits of comparative genomic analysis in the study of these pathogens. Overall the work is setting a stone raising questions about the pathogen N. seriolae. However, using as much information as needed would be of great importance to the overall objective of the study. Regarding reproducibility: It is not clear where the used code is deposited.
Please rate the manuscript for methodological rigour
Satisfactory
Please rate the quality of the presentation and structure of the manuscript
Satisfactory
To what extent are the conclusions supported by the data?
Strongly support
Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?
No
Is there a potential financial or other conflict of interest between yourself and the author(s)?
No
If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?
Yes
-
Comments to Author
The proposed methodological are appropriate for addressing the objectives. However, the analyses and interpretation of the results were discussed superficially. Given that the species is considered to have low genetic diversity, it would be more suitable to include higher-resolution analyses, such as variant calling, genomic rearrangements, or recombination analysis, considering the syntenic variation results. ANI analyses would not be sufficient to detect differences between strains . I recommend employing alternative methods for tree construction, such as maximum likelihood or Bayesian approaches. Details regarding strain-specific genes, accessory genes, and shared or unique genomic islands were not adequately discussed or annotated. Additionally, the presence of virulence genes was not described in …
Comments to Author
The proposed methodological are appropriate for addressing the objectives. However, the analyses and interpretation of the results were discussed superficially. Given that the species is considered to have low genetic diversity, it would be more suitable to include higher-resolution analyses, such as variant calling, genomic rearrangements, or recombination analysis, considering the syntenic variation results. ANI analyses would not be sufficient to detect differences between strains . I recommend employing alternative methods for tree construction, such as maximum likelihood or Bayesian approaches. Details regarding strain-specific genes, accessory genes, and shared or unique genomic islands were not adequately discussed or annotated. Additionally, the presence of virulence genes was not described in relation to specific strains or their phenotypes, which would have been valuable to reinforce the study objectives. Caution is needed with terms such as "strong correlation" (lines 203-204), which would be more appropriate to describe a statistically significant relationship. Did not show the relevant results (significance of the open pangenome, mobile elements, and sequence similarity results) in the abstract . Regarding the results, to show in the figures, Tables, strain names or accession numbers . Additionally, the figures lack proper formatting, sizes letters are not appropriate (Figure 3 and supplementary figures) In the section on single-copy phylogenomic studies, the phylogeny and ANI analyses could be better represented, as this would enhance the discussion of clustering and their relationship with phenotypic characteristics (e.g., host, countries, years, or other ecological traits). Furthermore, improved Supplementary Figures 1 and 3 could be main figures. The discussion is descriptive, general and lacks insights of the functional roles of specific genes. Furthermore, the interpretation of phylogenetic trees is not clear (lines 284, 289). The study highlight high level of genetic uniformity in the species ("a high degree of uniformity in their genomes"). However, Figure 2 shows substantial structural differences (e.g., inversions, translocations) between genomes, while Table 1 and Supplementary Figure 5 indicate variability in accessory genes. Other question is the ANI analysis alone not is sufficient to evaluate differences between strains. For this reason I suggest a substantial revision of manuscript.
Please rate the manuscript for methodological rigour
Satisfactory
Please rate the quality of the presentation and structure of the manuscript
Satisfactory
To what extent are the conclusions supported by the data?
Not at all
Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?
No
Is there a potential financial or other conflict of interest between yourself and the author(s)?
No
If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?
Yes
-
