Dear Dr Hay,

Thank you very much for submitting your manuscript "An open source tool to infer epidemiological and immunological dynamics from serological data: serosolver" for consideration at PLOS Computational Biology. As with all papers reviewed by the journal, your manuscript was reviewed by members of the editorial board and by several independent reviewers. The reviewers appreciated the attention to an important topic. Based on the reviews, we are likely to accept this manuscript for publication, providing that you modify the manuscript according to the review recommendations.

Please prepare and submit your revised manuscript within 30 days. If you anticipate any delay, please let us know the expected resubmission date by replying to this email. 

When you are ready to resubmit, please upload the following:

[1] A letter containing a detailed list of your responses to all review comments, and a description of the changes you have made in the manuscript. Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out

[2] Two versions of the revised manuscript: one with either highlights or tracked changes denoting where the text has been changed; the other a clean version (uploaded as the manuscript file).

Important additional instructions are given below your reviewer comments.

Thank you again for your submission to our journal. We hope that our editorial process has been constructive so far, and we welcome your feedback at any time. Please don't hesitate to contact us if you have any questions or comments.

Sincerely,

Roland R Regoes

Associate Editor

PLOS Computational Biology

Virginia Pitzer

Deputy Editor

PLOS Computational Biology

***********************

A link appears below if there are any accompanying review attachments. If you believe any reviews to be missing, please contact ploscompbiol@plos.org immediately:

[LINK]

Reviewer's Responses to Questions

Comments to the Authors:

Please note here if the review is uploaded as an attachment.

Reviewer #1: Thank you for addressing my previous comments. Very nice paper!

Very minor suggestion: I agree with the decision to use lower case consistently with the package name. However you can avoid starting sentences with 'serosolver' by slight rephrasing. For instance:

L58: serosolver takes assay results... -> The serosolver package takes assay results...

L178: serosolver tracks each individual's infection history as a... -> Each individual's infection history is tracked by serosolver as a...

Might help with the blood pressure of grammar nazi readers.

Reviewer #2: The authors did significant revisions of the manuscript in response to Reviewers comments.

All my concerns from my previous review of the manuscript have been addressed.

It is a well-written, well-organized paper describing nicely documented flexible R package serosolver that will be of interest for those aiming to dissect humoral immune responses to multi-strain pathogens like influenza. I strongly recommend it for publication.

Correction is needed for revised Fig 4B:

Lns 450-453: text refers to the Fig 4B with three age-specific exposure rates, while revised figure shows only two age groups. Corresponding figure legend refers to 3 groups but the green color for age 19-64 on the figure does not match the color indicated in the legend.

Reviewer #3: I previously reviewed this paper for PLoS Biology and suggested that PLoS Comp Bio might be the more suitable journal. The authors addressed all comments I provided on my previous review, I have no further ones.

One general comment, mainly meant for the editor: Instead of this being labeled a 'research article', it might be better to classify it as a 'software article' (or whatever terminology the journal uses).

**********

Have all data underlying the figures and results presented in the manuscript been provided?

Large-scale datasets should be made available via a public repository as described in the PLOS Computational Biology data availability policy, and numerical data that underlies graphs or summary statistics should be provided in spreadsheet form as supporting information.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

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

Reviewer #3: No

Figure 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. 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 us at figures@plos.org.

Data Requirements:

Please note that, as a condition of publication, PLOS' data policy requires that you make available all data used to draw the conclusions outlined in your manuscript. Data must be deposited in an appropriate repository, included within the body of the manuscript, or uploaded as supporting information. This includes all numerical values that were used to generate graphs, histograms etc.. For an example in PLOS Biology see here: http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001908#s5.

Reproducibility:

To enhance the reproducibility of your results, PLOS recommends that you deposit laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see http://journals.plos.org/ploscompbiol/s/submission-guidelines#loc-materials-and-methods

Dear Dr Hay,

We are pleased to inform you that your manuscript 'An open source tool to infer epidemiological and immunological dynamics from serological data: serosolver' has been provisionally accepted for publication in PLOS Computational Biology.

Before your manuscript can be formally accepted you will need to complete some formatting changes, which you will receive in a follow up email. A member of our team will be in touch with a set of requests.

Please note that your manuscript will not be scheduled for publication until you have made the required changes, so a swift response is appreciated.

IMPORTANT: The editorial review process is now complete. PLOS will only permit corrections to spelling, formatting or significant scientific errors from this point onwards. Requests for major changes, or any which affect the scientific understanding of your work, will cause delays to the publication date of your manuscript.

Should you, your institution's press office or the journal office choose to press release your paper, you will automatically be opted out of early publication. We ask that you notify us now if you or your institution is planning to press release the article. All press must be co-ordinated with PLOS.

Thank you again for supporting Open Access publishing; we are looking forward to publishing your work in PLOS Computational Biology. 

Best regards,

Virginia E. Pitzer, Sc.D.

Deputy Editor

PLOS Computational Biology

Virginia Pitzer

Deputy Editor

PLOS Computational Biology

***********************************************************