[REVIEW]: CPgeneProfiler: A lightweight R package to profile the Carbapenamase genes from genome assemblies

[whedon]

Submitting author: @ramadatta (Prakki Sai Rama Sridatta)
Repository: https://github.com/ramadatta/CPgeneProfiler
Version: v2.1.1
Editor: @will-rowe
Reviewer: @fmaguire, @boasvdp
Archive: 10.5281/zenodo.4076089

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Review checklist for @fmaguire

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• I confirm that I have read the JOSS conflict of interest (COI) policy and that: I have no COIs with reviewing this work or that any perceived COIs have been waived by JOSS for the purpose of this review.

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General checks

• Repository: Is the source code for this software available at the repository url?
• License: Does the repository contain a plain-text LICENSE file with the contents of an OSI approved software license?
• Contribution and authorship: Has the submitting author (@ramadatta) made major contributions to the software? Does the full list of paper authors seem appropriate and complete?
• Substantial scholarly effort: Does this submission meet the scope eligibility described in the JOSS guidelines

Functionality

• Installation: Does installation proceed as outlined in the documentation?
• Functionality: Have the functional claims of the software been confirmed?
• Performance: If there are any performance claims of the software, have they been confirmed? (If there are no claims, please check off this item.)

Documentation

• A statement of need: Do the authors clearly state what problems the software is designed to solve and who the target audience is?
• Installation instructions: Is there a clearly-stated list of dependencies? Ideally these should be handled with an automated package management solution.
• Example usage: Do the authors include examples of how to use the software (ideally to solve real-world analysis problems).
• Functionality documentation: Is the core functionality of the software documented to a satisfactory level (e.g., API method documentation)?
• Automated tests: Are there automated tests or manual steps described so that the functionality of the software can be verified?
• Community guidelines: Are there clear guidelines for third parties wishing to 1) Contribute to the software 2) Report issues or problems with the software 3) Seek support

Software paper

• Summary: Has a clear description of the high-level functionality and purpose of the software for a diverse, non-specialist audience been provided?
• A statement of need: Do the authors clearly state what problems the software is designed to solve and who the target audience is?
• State of the field: Do the authors describe how this software compares to other commonly-used packages?
• Quality of writing: Is the paper well written (i.e., it does not require editing for structure, language, or writing quality)?
• References: Is the list of references complete, and is everything cited appropriately that should be cited (e.g., papers, datasets, software)? Do references in the text use the proper citation syntax?

Review checklist for @boasvdp

Conflict of interest

• I confirm that I have read the JOSS conflict of interest (COI) policy and that: I have no COIs with reviewing this work or that any perceived COIs have been waived by JOSS for the purpose of this review.

Code of Conduct

• I confirm that I read and will adhere to the JOSS code of conduct.

General checks

• Repository: Is the source code for this software available at the repository url?
• License: Does the repository contain a plain-text LICENSE file with the contents of an OSI approved software license?
• Contribution and authorship: Has the submitting author (@ramadatta) made major contributions to the software? Does the full list of paper authors seem appropriate and complete?
• Substantial scholarly effort: Does this submission meet the scope eligibility described in the JOSS guidelines

Functionality

• Installation: Does installation proceed as outlined in the documentation?
• Functionality: Have the functional claims of the software been confirmed?
• Performance: If there are any performance claims of the software, have they been confirmed? (If there are no claims, please check off this item.)

Documentation

• A statement of need: Do the authors clearly state what problems the software is designed to solve and who the target audience is?
• Example usage: Do the authors include examples of how to use the software (ideally to solve real-world analysis problems).
• Installation instructions: Is there a clearly-stated list of dependencies? Ideally these should be handled with an automated package management solution.
• Functionality documentation: Is the core functionality of the software documented to a satisfactory level (e.g., API method documentation)?
• Automated tests: Are there automated tests or manual steps described so that the functionality of the software can be verified?
• Community guidelines: Are there clear guidelines for third parties wishing to 1) Contribute to the software 2) Report issues or problems with the software 3) Seek support

Software paper

• Summary: Has a clear description of the high-level functionality and purpose of the software for a diverse, non-specialist audience been provided?
• A statement of need: Do the authors clearly state what problems the software is designed to solve and who the target audience is?
• State of the field: Do the authors describe how this software compares to other commonly-used packages?
• Quality of writing: Is the paper well written (i.e., it does not require editing for structure, language, or writing quality)?
• References: Is the list of references complete, and is everything cited appropriately that should be cited (e.g., papers, datasets, software)? Do references in the text use the proper citation syntax?

[whedon]

Hello human, I'm @whedon, a robot that can help you with some common editorial tasks. @fmaguire, @boasvdp it looks like you're currently assigned to review this paper 🎉.

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[whedon]

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[whedon]

Reference check summary:

OK DOIs

- None

MISSING DOIs

- https://doi.org/10.1093/bioinformatics/btx364 may be missing for title: UpSetR: an R package for the visualization of intersecting sets and their properties
- https://doi.org/10.1186/1471-2105-10-421 may be missing for title: BLAST+: architecture and applications
- https://doi.org/10.1186/s13073-014-0090-6 may be missing for title: SRST2: rapid genomic surveillance for public health and hospital microbiology labs
- https://doi.org/10.1093/jac/dks261 may be missing for title: Identification of acquired antimicrobial resistance genes
- https://doi.org/10.1093/nar/gkw1009 may be missing for title: MEGARes: an antimicrobial resistance database for high throughput sequencing
- https://doi.org/10.1093/nar/gkw1004 may be missing for title: CARD 2017: expansion and model-centric curation of the comprehensive antibiotic resistance database
- https://doi.org/10.1128/aac.01310-13 may be missing for title: ARG-ANNOT, a new bioinformatic tool to discover antibiotic resistance genes in bacterial genomes
- https://doi.org/10.1099/mgen.0.000131 may be missing for title: ARIBA: rapid antimicrobial resistance genotyping directly from sequencing reads
- https://doi.org/10.3389/fpubh.2019.00242 may be missing for title: Using genomics to track global antimicrobial resistance
- https://doi.org/10.1093/ofid/ofx176 may be missing for title: Prevalence of carbapenem-resistant Gram-negative infections in the United States predominated by Acinetobacter baumannii and Pseudomonas aeruginosa
- https://doi.org/10.1016/j.jinf.2018.11.003 may be missing for title: Whole genome sequencing detects inter-facility transmission of carbapenem-resistant Klebsiella pneumoniae
- https://doi.org/10.1128/aac.02282-18 may be missing for title: Cocarriage of distinct blaKPC-2 and blaOXA-48 plasmids in a single sequence type 11 carbapenem-resistant Klebsiella pneumoniae isolate
- https://doi.org/10.1093/cid/ciz824 may be missing for title: Epidemiology and diagnostics of carbapenem resistance in gram-negative bacteria

INVALID DOIs

- None

[will-rowe]

@ramadatta - please can you add the flagged DOIs to your paper references

[ramadatta]

@ramadatta - please can you add the flagged DOIs to your paper references

@will-rowe, @boasvdp, @fmaguire Thank you so much for kindly agreeing to review the submission!

@will-rowe - I have added the missing DOIs in the paper now and tested the build.

[fmaguire]

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[whedon]

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[fmaguire]

Overview

In this tool the author's provide an R package that generates some potentially useful diagnostic plots for AMR researchers with limited data analysis/visualisation experience and an interest in carbapenemase genes.
Unfortunately, the utility of this tool is currently hampered by its lack of modularity, choice of AMR database, and limited ease of installation/dependency management.
While there are no existing AMR detection tools that do exactly the same summary/analysis that this package provides, there are several that provide more comprehensive AMR profiling (more than just carbapenemases), some visualisation, and generation of outputs that can be visualised as the analyst sees fit with relatively little work.

With improved documentation, a fairly major overhaul to improve modularity and packaging (listed below) CPgeneProfiler could represent a handy set of visualisation utilities for this targeted research/public health group.
However, as it currently stands CPgeneProfiler isn't widely applicable outside the specific internal analytical use-case for which it was developed.

Installation

• Major: Installation procedure needs streamlining (using dependency management to handle installation of required R packages): issue
• Minor: Few minor typos in README and installation instructions, fixed in PR

Functionality

• Major: Generated plots don't contain assembly names so main utility of comparison of CP genes across assemblies is limited until this is fixed e.g. heatmap y-axis labels: issue
• Major: Entire package is a single function greater limiting utility/flexibility: issue
• Major: Built around ARG-ANNOT (not hard to change), no updates/curation in >2 years therefore CPGeneProfiler cannot be used for surveillance of many novel CP alleles: issue
• Minor: Artefacts and unspecific labels in some plots: issue also mentioned in issue
• Minor: Typo in output filename: issue

Documentation

• Major: R package DESCRIPTION file metadata needs completed: issue
• Minor: README citations need fixed: issue
• Minor: Example usage is sufficient although could be further fleshed out.
• Minor: Test data but no automated tests: issue
• Minor: No community guidelines: issue

Software Paper

• Major: Paper and documentation doesn't really explain the specific utility of each output of tool: issue
• Minor: Should clarify that not all OXA beta-lactamases are CP genes: issue
• Minor: Manuscript conflates AMR databases and AMR gene detection tools: issue
• Minor: References need added/updated for AMR databases/tools: issue
• Minor: Comparison to more comprehensive AMR detection tools with summary plots etc needs added and benefits of CPgeneProfiler's specialisation clearly stated: issue

[ramadatta]

@fmaguire We sincerely appreciate your comprehensive review. We will go through each of them and come back at the earliest. Thank you!

[will-rowe]

Thanks @fmaguire - that's an excellent review.

@ramadatta - feel free to begin working on these points now. @boasvdp will also be providing feedback so please keep an eye out for that too.

I'm due to go on annual leave for a week next week. I'll check back in here when I'm back but please ping another editor if you need assistance next week.

[ramadatta]

@will-rowe Sure. Thank you very much!

[boasvdp]

Hi all,

I'm on annual leave at this moment, but will be back in a week. I'll do the review before the end of next week (July 24).

@ramadatta Are there any specific things you'd like extra feedback/attention on?

[ramadatta]

@boasvdp Thank you very much! Nothing specific for me at the moment. Will begin working on with @fmaguire points.

[boasvdp]

General

The described tool identifies carbapenemase genes from assembled bacterial genomes and produces additional plots, especially aimed at co-carriage. The identification of carbapenemase genes is possible through other tools, but I am unaware of any tools which produce the additional plots that are included in the CPgeneProfiler output. The tool is installable (although this could be improved) and does what it promises. However, improvements are possible and in some cases necessary.

One major outstanding question for me is the 'audience' for this software. What level of bioinformatics expertise would you expect for people using your tool? Is this a tool for bioinformaticians, or is this intended for molecular biologists with some R experience? This influences some of the suggestions I have made below, as some will apply more or less depending on the bioinformatics expertise of the audience you're aiming for.

I support all notions made by @fmaguire above, and will try to provide additional feedback where needed.

Installation

• I second the @fmaguire's idea to make a (bio)conda package, as all dependencies are already available in conda. Otherwise, automated handling of dependencies would be good.

Functionality

• Summary report, especially helpful for researchers without a lot of bioinformatics expertise: FUNCTIONALITY: Inclusion of a summary report ramadatta/CPgeneProfiler#21
• As @fmaguire noted, having the possibility to run the tool in a modular way would be helpful (if the tool is aimed at bioinformaticians)
• The addition of some extra options would improve the tool, esp. regarding output (FUNCTIONALITY: Adding option for output location ramadatta/CPgeneProfiler#22) and blastn thresholds (FUNCTIONALITY: Blastn thresholds for CP gene identification ramadatta/CPgeneProfiler#23)
• ARG-ANNOT is not regularly updated, using a better database (or ideally multiple databases) would improve the tool. NCBI has a regularly updated database: https://www.ncbi.nlm.nih.gov/pathogens/isolates#/refgene/

Documentation

• There is no source provided for the delineation of carbapenemase genes: DOCUMENTATION: No source provided for the delineation of CP genes ramadatta/CPgeneProfiler#24
• There is no clear mention of the default settings: DOCUMENTATION: Default blastn settings are not indicated ramadatta/CPgeneProfiler#25

Software paper

• Currently, there is no comparison with other tools. Due to the strict treshold used by CPgeneProfiler, this could lead to a lower sensitivity, esp. with misassemblies/sequencing errors/new alleles. If custom thresholds are added as an option, I would not expect too many differences with other tools as these are mostly based on blast as well. I have not opened an issue for this one as I expect this will resolve itself.

[ramadatta]

@boasvdp - Thank you so much for the comments!

I actually intended to make this package helpful to biologists who have only little experience in R. I am working on the package currently and trying to make it modular. I also appreciate both of your suggestions on changing the database and working on this. I am making an effort to make the functionality more flexible. Thanks again!

[will-rowe]

Thank you very much for your review @boasvdp.

@ramadatta - please let us know when you have had chance to respond to these comments and are ready for us to take another look over your submission.

[will-rowe]

Hey @ramadatta - can you let me know how you are getting on please? No pressure, just chasing up!

[ramadatta]

Thanks @will-rowe - I am almost done with the comments on functionality from both the authors. I am working on installation portion.

[will-rowe]

Hi @ramadatta - just another ping to see how you are getting on?

[ramadatta]

Hi @will-rowe - thank you. I am in the process of documenting the package. Once I am done with this, I will start editing the final paper possibly this weekend and aim to submit soon.

[ramadatta]

Hi @will-rowe - just an update on manuscript. I am almost done with manuscript and awaiting my collaborator's go-ahead to submit. Thank you.

[will-rowe]

Hi @ramadatta - just checking in again to see how you are progressing? Thanks!

[ramadatta]

Dear @will-rowe - Due to some unforeseen circumstances, I am not able to submit the manuscript within the timeframe expected before. I sincerely apologize for this delay. If it is possible, could I kindly request an extension for a week or two? Thank you very much for your consideration.

[will-rowe]

That's fine from my point of view. I'll check back in a couple of weeks unless I hear from you sooner

[ramadatta]

Thanks so much @will-rowe for understanding.

[ramadatta]

Sorry - missed the question re. editing. Sure you can - I will wait before flagging this paper to the editor in chief. Let me know when you are ready for the paper to be accepted. You will need another release/DOI if you make edits, so let me know what they are.

Thank you very much @will-rowe - I just made a minor edit at visualize the set intersections of cocarriage of CP genes in the manuscript.

Also, as you suggested, I have updated the CPgeneProfiler v2.1.1 release and updated the Zenodo repo author list. Thank you so much for the Bioconda request.

Please let me know if I missed anything else from my side. Else, I kindly request the editor for the manuscript to accepted.

[will-rowe]

@whedon set 10.5281/zenodo.4076089 as archive

[whedon]

OK. 10.5281/zenodo.4076089 is the archive.

[will-rowe]

@whedon accept

[whedon]

Attempting dry run of processing paper acceptance...

[whedon]

Reference check summary (note 'MISSING' DOIs are suggestions that need verification):

OK DOIs

- 10.3389/fmicb.2020.00052 is OK
- 10.1093/nar/gkz935 is OK
- 10.1093/jac/dkx217 is OK
- 10.1093/jac/dkaa345 is OK
- 10.1093/jac/dkw184 is OK
- 10.1186/s12859-018-2336-6 is OK
- 10.1093/bioinformatics/btx364 is OK
- 10.1186/1471-2105-10-421 is OK
- 10.1186/s13073-014-0090-6 is OK
- 10.1093/jac/dks261 is OK
- 10.1093/nar/gkw1009 is OK
- 10.1093/nar/gkz1010 is OK
- 10.1093/nar/gkw1004 is OK
- 10.1128/aac.01310-13 is OK
- 10.1099/mgen.0.000131 is OK
- 10.3389/fpubh.2019.00242 is OK
- 10.1093/ofid/ofx176 is OK
- 10.1016/j.diagmicrobio.2012.11.009 is OK
- 10.1128/AAC.00296-11 is OK
- 10.1016/j.jinf.2018.11.003 is OK
- 10.1128/genomeA.00199-18 is OK
- 10.1128/aac.02282-18 is OK
- 10.1093/cid/ciz824 is OK
- 10.1128/JCM.02086-16 is OK

MISSING DOIs

- None

INVALID DOIs

- None

[whedon]

👋 @openjournals/joss-eics, this paper is ready to be accepted and published.

Check final proof 👉 openjournals/joss-papers#1801

If the paper PDF and Crossref deposit XML look good in openjournals/joss-papers#1801, then you can now move forward with accepting the submission by compiling again with the flag deposit=true e.g.

@whedon accept deposit=true

[danielskatz]

Hi - I'm the JOSS AEiC this week, and I'll be finishing the processing of your submission. There are some wording problems in the paper - please either merge ramadatta/CPgeneProfiler#26 or let me know what you disagree with. In addition, a number of the references have case issues - please be sure all journals are in Title Case - use {}s in the bib file to protect cases as needed.

[ramadatta]

Dear @danielskatz - Thank you very much!

All the edits you made are completely acceptable for us, except the following:

In line 69: Following the terminology in the literature, we want it to be: set intersections

In line 73: N50, N90 and assembly size are 3 different statistics. So, it should be:
CPgeneProfiler can also generate the N50, N90 and assembly size statistics for each of the genome assemblies.

We did a careful recheck about the case issues of the tools that were referred in the manuscript. We understand we are following the same name convention of the tool as the authors published. Sorry, but could i kindly clarify what you meant by this? Thanks much!

[danielskatz]

I've changed the 2 things you disagreed with - please see if this is now ok, and if so, please merge.

[danielskatz]

Re cases, I've just gone ahead with ramadatta/CPgeneProfiler#27 - please merge this as well, or again, let me know what you disagree with

[ramadatta]

Re cases, I've just gone ahead with ramadatta/CPgeneProfiler#27 - please merge this as well, or again, let me know what you disagree with

Thank you @danielskatz - I have merged both the updates. Please let us know if anything else.

[danielskatz]

@whedon accept

[whedon]

Attempting dry run of processing paper acceptance...

[whedon]

Reference check summary (note 'MISSING' DOIs are suggestions that need verification):

OK DOIs

- 10.3389/fmicb.2020.00052 is OK
- 10.1093/nar/gkz935 is OK
- 10.1093/jac/dkx217 is OK
- 10.1093/jac/dkaa345 is OK
- 10.1093/jac/dkw184 is OK
- 10.1186/s12859-018-2336-6 is OK
- 10.1093/bioinformatics/btx364 is OK
- 10.1186/1471-2105-10-421 is OK
- 10.1186/s13073-014-0090-6 is OK
- 10.1093/jac/dks261 is OK
- 10.1093/nar/gkw1009 is OK
- 10.1093/nar/gkz1010 is OK
- 10.1093/nar/gkw1004 is OK
- 10.1128/aac.01310-13 is OK
- 10.1099/mgen.0.000131 is OK
- 10.3389/fpubh.2019.00242 is OK
- 10.1093/ofid/ofx176 is OK
- 10.1016/j.diagmicrobio.2012.11.009 is OK
- 10.1128/AAC.00296-11 is OK
- 10.1016/j.jinf.2018.11.003 is OK
- 10.1128/genomeA.00199-18 is OK
- 10.1128/aac.02282-18 is OK
- 10.1093/cid/ciz824 is OK
- 10.1128/JCM.02086-16 is OK

MISSING DOIs

- None

INVALID DOIs

- None

[whedon]

👋 @openjournals/joss-eics, this paper is ready to be accepted and published.

Check final proof 👉 openjournals/joss-papers#1805

If the paper PDF and Crossref deposit XML look good in openjournals/joss-papers#1805, then you can now move forward with accepting the submission by compiling again with the flag deposit=true e.g.

@whedon accept deposit=true

[danielskatz]

@whedon accept deposit=true

[whedon]

Doing it live! Attempting automated processing of paper acceptance...

[whedon]

🐦🐦🐦 👉 Tweet for this paper 👈 🐦🐦🐦

[whedon]

🚨🚨🚨 THIS IS NOT A DRILL, YOU HAVE JUST ACCEPTED A PAPER INTO JOSS! 🚨🚨🚨

Here's what you must now do:

0. Check final PDF and Crossref metadata that was deposited 👉 Creating pull request for 10.21105.joss.02473 joss-papers#1806
1. Wait a couple of minutes to verify that the paper DOI resolves https://doi.org/10.21105/joss.02473
2. If everything looks good, then close this review issue.
3. Party like you just published a paper! 🎉🌈🦄💃👻🤘

Any issues? Notify your editorial technical team...

[danielskatz]

Congratulations to @ramadatta (Prakki Sai Rama Sridatta) and co-authors!!

Thanks to editor @will-rowe and reviewer: @fmaguire & @boasvdp!

[whedon]

🎉🎉🎉 Congratulations on your paper acceptance! 🎉🎉🎉

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[ramadatta]

We are thoroughly impressed with JOSS editors and the review process.

We are very thankful to @fmaguire @boasvdp and @will-rowe for their comprehensive reviews and guidance.

Thanks @danielskatz for the wording in the final manuscript.