Peer Review History
Original SubmissionNovember 2, 2022 |
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PONE-D-22-30239A macroecological perspective on genetic diversity in the human gut microbiomePLOS ONE Dear Dr. Shoemaker, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. In particular, there are a number of writing issues to be addressed, and how the manuscript presents new results that contribute to the field. Please submit your revised manuscript by May 21 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. Please include the following items when submitting your revised manuscript:
If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols. We look forward to receiving your revised manuscript. Kind regards, Karthik Raman, Ph.D. Academic Editor PLOS ONE Journal requirements: When submitting your revision, we need you to address these additional requirements. 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf. 2. Thank you for stating the following in the Acknowledgments Section of your manuscript: “This work was supported by the NSF Postdoctoral Research Fellowships in Biology Program under Grant No. 2010885 (W.R.S.). This work used computational and storage services associated with the Hoffman2 Shared Cluster provided by UCLA Institute for Digital Research and Education’s Research Technology Group.” We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form. Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows: “This work was supported by the NSF Postdoctoral Research Fellowships in Biology Program under Grant No. 2010885 (W.R.S.). https://beta.nsf.gov/funding/opportunities/postdoctoral-research-fellowships-biology-prfb The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.” Please include your amended statements within your cover letter; we will change the online submission form on your behalf. 3. Please upload a copy of Figure 5, to which you refer in your text on page 17. If the figure is no longer to be included as part of the submission please remove all reference to it within the text. Additional Editor Comments: The reviews for the manuscript are in. While the reviewers found interesting aspects of your work, they have raised major concerns. Please revise the manuscript taking into consideration the reviews of both the reviewers. [Note: HTML markup is below. Please do not edit.] 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: No Reviewer #2: Yes ********** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: No Reviewer #2: Yes ********** 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: No Reviewer #2: Yes ********** 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: No Reviewer #2: Yes ********** 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: This manuscript by William Shoemaker explores intraspecies diversity within and across individual microbiomes, with a focus on the applicability of stochastic logistic model and the existence of strain structure. It is my understanding that the main result of this paper is that the result of this modeling is that strains (ecology) are responsible for more within-host variants than mutation (evolution). This result echoes the current thinking in the field, which has been shown before by other papers, including at least one on which this author is a contributor. This manuscript is difficult to read – partly because what is done is frequently described before what is the goal of this work is, and partly because concepts are a bit muddled / poorly introduced. I list some examples below. I also have some issues with data analysis. Most critically, it is hard to understand what is new in this paper. While it is my understanding that novelty is not a criterion for publication, more fully placing work in the context of the literature is very important for any theoretical or modeling based paper. Writing issues: It hard to understand from the abstract, introduction, text, and discussion, exactly is new in this manuscript. The introduction spends much time opining on the value and need for models, without really explaining what has been shown before about the SLM in microbiomes. In particular, the manuscript cites works, including from this author, showing that strains are responsible for most intraspecies dynamics in the microbiome (this has been known for quite some time) and SLMs describe these dynamics well. What was the open question the other set out to solve? If there was some doubt about the applicability of the SLM model and strains prior to this work, what was the critical missing analysis? What required the need for this approach? It requires a lot of work for a reader to understand what is being referred to at each point in the text. For example: • At Line 94: “the empirical distribution” is unclear; “the distribution of within-host allele frequencies across all hosts” would be clearer. Even clearer would be “the distribution of within-host frequencies at a given site, across all hosts” or something else. • Line 339: “unlikely for the allele frequency fluctuations I was able to observe”. Does this refer to fluctuations across hosts, or time? At the very least, a figure panel should be referred to here. • Line 418: what is a “true strain absence”. Is the author suggesting that single strain colonization is rare for all species and strains? This would conflict with the literature (e.g. B fragilis almost always colonizes humans as a single strain, PMID: 30673701), but if it is supported by the data this should be made more clear. • Line 104: which variable? Mean and variance across what? Line 500: I’m not sure exactly what point is trying to be made here. If there is already an interpretation of the data (antibiotics wiped out a strain), how does the SLM help? Technical notes: I find Figure 1 (as well as some s to not be presented in a manner such that I can evaluate the claim being made: that the rescaled distributions are similar across species. To evaluate this, I would like to see example distributions (perhaps cumulative curves) drawn for each species – instead what I am presented with is a mess of dots on top of each other in 1b and 1d. I see notable differences, even though these are rescaled already. No goodness of test fits are applied and no alternative distributions are provided. Site frequency spectra are not widely used in microbiology, as the SFS is something that results from recombination. The idea that within-host or across-host evolution would result in a meaningful SFS is confusing to this reviewer. Fig 2c: I’m not sure what the value of predicting “mean within-host allele frequency across hosts” is, if all hosts—including those without the allele at all—are included. Perhaps I am missing something. Also, it seems like most of the data here isn’t fitting the line, but instead fitting a curve starting at y = 10^-1. These graphs should be made as density maps to make it clearer how well the data and the prediction line up. Some thoughts: It is clear that the author has put a lot of work into the generation of this data and model, but it is always important to be clear about what is known and what is novel. The formalization of an already proposed model can be valuable. Presenting a model which more clearly shows what has been shown by others could also be valuable; if this is the goal than more effort needs to be put into making it clear. Reviewer #2: In this work, the author used a statistical approach to a publicly available metagenomic dataset to evaluate the dynamics of genetic diversity in the human gut microbiome. They used a proposed distribution of allele frequencies to predict the prevalence of a given allele in a given species in a host. They found that the Stochastic Logistic Model accurately predicted this across species, and could also predict the prevalence of alleles across multiple hosts. Generally, this is an interesting work. However, as someone with a limited background in biostatistics, I find the description of the underlying modeling approach very hard to follow. For instance, the assumptions behind the SLM described from line 197-208 are not clear to me. Hence, my recommendation is to clarify the description of the SLM, its assumptions, and the overall discussed concepts for readers less familiar with them. I understand that this is not my area of expertise, but it would be very helpful to make the presented results more accessible to scientists in the gut microbiome field. Minor comments: - The legends for Figures 1-4 are more a repetition of the Results section than a clear description of what is shown in each panel. - Line 339: MAGPD is mentioned here for the first time without having been defined before. - Line 448-449: “Regardless of the speci c model, the conclusion that a substantial fraction of observable alleles are primarily subject to ecological, as opposed to evolutionary, dynamics is of consequence to studies of genetic diversity in the human gut.” It is not clear to me which part of the Results section precisely shows this. - Line 655: There is a figure legend for Figure 5, which dos not exist. - Line 704: Is this really the correct URL for the Human Microbiome Project? ********** 6. 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 ********** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. 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Revision 1 |
PONE-D-22-30239R1A macroecological perspective on genetic diversity in the human gut microbiomePLOS ONE Dear Dr. Shoemaker, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by Jul 06 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. Please include the following items when submitting your revised manuscript:
If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols. We look forward to receiving your revised manuscript. Kind regards, Karthik Raman, Ph.D. Academic Editor PLOS ONE Additional Editor Comments: I am in agreement with one of the reviewers, who has given detailed constructive criticism to further improve the manuscript. It is important that the manuscript be carefully revisited to systematically address all the concerns of the reviewers. [Note: HTML markup is below. Please do not edit.] 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: (No Response) Reviewer #2: All comments have been addressed ********** 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: Partly Reviewer #2: Yes ********** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: I Don't Know Reviewer #2: (No Response) ********** 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 ********** 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: No Reviewer #2: 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: This manuscript has improved from the last version. In R2R document, the author states that the purpose of this manuscript is to demonstrate that the previously proposed model, in which (1) most intrastrain polymorphisms arise from migration and growth of strains rather than within-person evolution; and (2) this is formalized with an SLM model, can explain allelic prevalence across hosts. Bolstering the SLM model and the importance of strain structure is a fine goal (though I have a question on the contextualization of this below), and now I can begin to interpret the manuscript. Significant work still remains to be done on the writing side. While the author appears to have attempted to address my concerns, shortcuts were taken rather than addressing the real problem (e.g. point #1f below), the text still falls short of communicating what is being advanced by these models, and murky language is used throughout--- such that I still relied heavily on the response to the reviewer (R2R) to interpret what the author intended. I do not think that all interdisciplinary work needs to be so difficult to read. I also have major concerns around the framing and some technical aspects of this work. 1) The writing is murky and it is hard to follow what point the author is making throughout. 1a) As an example to the author, I provide below an edited alternative of the middle of the abstract which is easier to read. In this example, the connection between strains and ecology is made more clear to a naiive reader, and what the SLM is modeling (strains) is made clear within the sentence that introduces it. The use of a “however” is removed from a location where a clear contrast isn’t being made. The phrases “determine whether” and “is capable of capturing” are replaced by more direct language. I am not sure if the suggestion for the last sentence reflects what the author intended; if I am incorrect, the author should clarify what is meant by “patterns of genetic diversity across hosts follow statistically similar forms”. Revised abstract: “…Recent efforts have suggested that a large fraction intrahost, intraspecies, genetic variation is driven by dynamics between co-colonizing of strains of the same species, highlighting the importance of modeling ecological forces. In particular, the Stochastic Logistic Model (SLM) of growth, commonly used in macroecology to describe between-species variation, has been used successfully to predict the temporal dynamics of strains within a single human host. Here, using data from 22 common microbial species across a large cohort of unrelated hosts, I show that the SLM also successfully predicts across-host genetic diversity in the human gut. The SLM predicts both the distribution of allele frequencies across hosts and the fraction of hosts harboring an allele for a given site (i.e., prevalence). The accuracy of the SLM in predicting these across-host parameters is correlated with independent estimates of strain structure, confirming that the success of the SLM arises from the presence of strain-level ecology in the human gut. 1b) In regards to my point #2 in the previous round the authors have changed a phrase but have not fixed the core of the problem, which is requiring a reader to read every sentence in order and guess what is being referred to be able to follow. One should not write “allele frequency fluctuations that I was able to observe” when they could say something like “THE LARGE allele frequency fluctuations ACROSS HOSTS” or whatever feature the author is actually intending here. As a reader, I cannot evaluate the validity of a sentence that is vague. 1c) Line 62 would be clearer if the manuscript said “In macroecology, the SLM…. “ 1d) The last paragraph of the introduction would be much clearer with specific methods (is “an ecological model” different than the SLM already discussed? In the last sentence, what is “an alternative evolutionary model”?) or with the general methods removed (just state result). 1e) “First, I examined the distribution of within-host allele frequencies across hosts.” This should be explained better. This is not a normal metric, and it would be great if this could be spelled out. 1f) Line 70: “If the typical allele was present due to evolutionary forces, then the empirical distribution of within-host allele frequencies across hosts can be viewed as an ensemble of single-site frequency spectra.” By definition I believe that this metric is an ensemble of SFS. I think you mean “… across hosts WOULD BE EQUIVALNT TO THE ensemble of single-site frequency spectra EXPECTED FROM WITHIN PERSON EVOLUTION.” It would also be helpful for the reader if the shape of each of these expectations were described in terms of the distributions used in Figure 1 in this paragraph. 1g) The dN/dS curve mentioned is all for Bacteroides and related species. This curve has not been investigated in other major taxa (e.g. Clostridia). In addition, this result is mentioned but not explained well enough for a reader to understand this point. “a clear example being the observation 41 that THE RATIO OF NONSYNONYMOUS DIVERGENCE TO SYNONYMOUS DIVERGENCE DECAYS NEARLY IDENTICALLY OVER LONG TIME SCALES OF across microbial species in the human gut” 1h) “This disproportionate focus on 32 individual species and differences between species can lead to idiosyncratic notions 33 about the typical dynamics of a genetic variant in the microbiome….. Instead, it is reasonable to start by identifying genetic patterns” I am just not sure what this means. One interpretation of these sentences is that the author is claiming that looking at things one species at a time is incorrect. I’m not sure the author needs to say this. I think it would be enough to say that identifying a single model that works across species would reveal general principles of eco-evo dynamics across microbiomes. There are parts of the results section that are likewise confusing, but I have selected to use my time to give several clear examples of areas for improvement in the introduction and results as an example to the author of how more clarity can be achieved. Other major concerns: 2) It is very true that new and better eco-evo models are needed for microbial populations, but the presentation of current knowledge in the population genetics field and the remaining gaps are incorrectly summarized. 2a) The surprise of strain structure is a bit overstated. One can infer that strains are a real entity by building phylogenetic trees from available isolates or from metagenomic samples with single strains (e.g. quasiphasable as in Garud and Good et al). This sort of expectation should be more explicitly stated in the introduction. 2b) Page 2, Line 20: “Such dynamics are a clear departure from those captured by standard population genetic models, where genetic variants either arise in a population due to mutation or are introduced by migration and then proceed 22 towards extinction or fixation (i.e., origin-fixation models), suggesting that measures of genetic diversity estimated within the human gut are shaped by the ecology of strains alongside evolution [10]. “ There are many population genetic models that deal with standing variation – the entire field of human population genetics on quantitative traits comes to mind. I think the bigger gap is that models for population genetics on standing variation don’t deal with the genome-wide linkage inherent to bacteria. 2c) “This confluence of ecological and evolutionary dynamics calls into question the 26 feasibility of characterizing genetic diversity in the human gut.” “Calls into question the feasibility” is a bit overstated. How about “requires new approaches and theory for” 3) I am not swayed by the argument that there are always multiple strains in a subject (response to previous point #3). B fragilis is often found at very high abundances, and the presences of strain structure does not correlate with the abundance in that species, as would be expected if there was a detection limit problem. The author has not proved “a lack of genuine absences of strain structure” which is very strong claim that when not written in the double negative. This could be mitigated by putting a qualifier of “for most species” for most sentences in this paragraph. 4) If I am understanding correctly, this paper is about the cross-host applicability of the SLM. However, the examples in the last paragraph of the discussion are all about within-host dynamics, which were investigated in a prior manuscript. This is confusing and perhaps misleading. Could the across-host applicability of the SLM help us understand how the microbiome at a global scale might change in response to a global perturbation like global warming? 5) I understand that Figure 1 isn’t about a goodness of fit, though the author has now done some analysis in this direction now anyway. I still don’t really understand what I am supposed to learn from this data looking roughly gamma though. How do the lognormal and gamma distribution relate to the SFS expected for within-host evolution described in lead up to Figure 1? Can the author give an example of a generative process that wouldn’t result in the patterns shown in Figure 1? Reviewer #2: In their revision, the author worked to improve the readability of the manuscript, clarifying the concepts and the aim of the study. Overall, they did a good job. I thank the author for rewriting the manuscript to make it easier to follow. KI still have some difficulties interpreting the equations, which is likely due to my unfamiliarity with the subject. Overall comments: - Since the article was based on a previously published work (Wolff et al. 2023), I think it would improve understanding of the context of the study further if one or two lines summarizing the results of that study were added at line 69. - While the last paragraph of the discussion addresses this, it is still not entirely clear to me how the model can be applied to dysbiosis. What are the implications of the prediction of the prevalence of a given gene in a fraction of hosts? What does that tell us about the microbiome? ********** 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 ********** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. |
Revision 2 |
PONE-D-22-30239R2A macroecological perspective on genetic diversity in the human gut microbiomePLOS ONE Dear Dr. Shoemaker, Thank you for submitting your manuscript to PLOS ONE. The manuscript is now almost ready for acceptance. However, we have a new reviewer, who has a minor comment, which the author could potentially comment on, and further improve the manuscript. Please submit your revised manuscript by Aug 16 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. Please include the following items when submitting your revised manuscript:
If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols. We look forward to receiving your revised manuscript. Kind regards, Karthik Raman, Ph.D. Academic Editor PLOS ONE Journal Requirements: Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. [Note: HTML markup is below. Please do not edit.] 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 #3: All comments have been addressed ********** 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 #3: Yes ********** 3. Has the statistical analysis been performed appropriately and rigorously? 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 #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 #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 #3: The author has addressed all prior reviewer concerns. I have no further concerns, and I commend the author on an interesting piece. One minor point that the author may want to consider is to discuss de novo evolution of coexisting strains from a recent ancestor within the lifespan of a human host. Most of the discussion of ecological dynamics of strains appears to assume rather distant lineages (separated by > thousands of SNPs) colonizing the same host. However, the Zhao et al. reference (ref 1) shows two B. fragilis strains within an individual, separated by a handful of SNPs, where both lineages coexist for a year or more (i.e., stationary dynamics - one lineage does not sweep the other). This would suggest a kind of sympatric speciation (transition from the evolutionary to the ecological regime) is possible over very short timescales. ********** 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 #3: No ********** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. |
Revision 3 |
A macroecological perspective on genetic diversity in the human gut microbiome PONE-D-22-30239R3 Dear Dr. Shoemaker, 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. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Karthik Raman, Ph.D. Academic Editor PLOS ONE |
Formally Accepted |
PONE-D-22-30239R3 A macroecological perspective on genetic diversity in the human gut microbiome Dear Dr. Shoemaker: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Karthik Raman Academic Editor PLOS ONE |
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