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peer review: 1 approved, 1 approved with reservations].","volume":"10","author":"F M\u00f6lder","year":"2021","journal-title":"F1000Res."},{"key":"ref-14","first-page":"29-32","article-title":"Using cron and crontab.","volume":"2","author":"L Reznick","year":"1993","journal-title":"Sys Admin."},{"key":"ref-15","article-title":"grinch_config.yaml [Data set].","author":"A O'Toole","year":"2021","journal-title":"Zenodo."},{"key":"ref-16","doi-asserted-by":"publisher","DOI":"10.1101\/2020.11.10.20228528","article-title":"Two-step strategy for the identification of SARS-CoV-2 variants co-occurring with spike deletion H69-V70, Lyon, France, August to December 2020","author":"A Bal","year":"2020","journal-title":"bioRxiv."},{"key":"ref-17","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1038\/s41597-020-00688-8","article-title":"A cross-country database of COVID-19 testing.","volume":"7","author":"J Hasell","year":"2020","journal-title":"Sci Data."},{"key":"ref-18","doi-asserted-by":"publisher","first-page":"533-4","DOI":"10.1016\/S1473-3099(20)30120-1","article-title":"An interactive web-based dashboard to track COVID-19 in real time.","volume":"20","author":"E Dong","year":"2020","journal-title":"Lancet Infect Dis."},{"key":"ref-19","article-title":"Supplementary materials with group affiliations for Tracking the international spread of SARS-CoV-2 lineages B.1.1.7 and B.1.351\/501Y-V2.","author":"A O'Toole","year":"2021","journal-title":"Zenodo."}],"container-title":["Wellcome Open Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/6-121\/v2\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/6-121\/v2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/6-121\/v2\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,20]],"date-time":"2021-09-20T14:45:39Z","timestamp":1632149139000},"score":1,"resource":{"primary":{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/6-121\/v2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,17]]},"references-count":19,"URL":"https:\/\/doi.org\/10.12688\/wellcomeopenres.16661.2","relation":{},"ISSN":["2398-502X"],"issn-type":[{"value":"2398-502X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,17]]},"assertion":[{"value":"Indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/6-121\/v2#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.21956\/wellcomeopenres.18372.r43966, Rob Lanfear, Department of Ecology and Evolution, Research School of Biology, Australian National University, Canberra, ACT, Australia, 27 May 2021, version 1, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/6-121\/v1#referee-response-43966","order":0,"name":"referee-response-43966","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>&Aacute;ine Niamh O'Toole<\/b>; \n<i>Posted: 10 Sep 2021<\/i>; Thank you so much for your detailed review and our apologies for not responding sooner. All your comments were well justified and fair. We've responded to and believe have addressed your comments and concerns below.&nbsp;  \n<i>I felt there was some tension in this article about whether it\u2019s a software note or a public health report. The title suggests the latter, but much of the article (and the article type of \u201cSoftware Tool Article\u201d) suggests the former. Most of this tension for me as a reader came from looking at the title, which has no mention of software, so I think sets up expectations that differ from what is then provided (quite reasonably) in the paper. A very simple way to address this would be to start the title with \u201cUsing grinch to track\u2026\u201d or to end it with \u201c\u2026 using grinch\u201d.<\/i>  I completely agree, it\u2019s a very fair point! We had originally submitted the article as a public health report but this didn\u2019t fit with the Wellcome Open Research journal remit, so resubmitted under Software Tool. I have changed the title as suggested to with with \u201cusing grinch\u201d.  \n<i>Similar to point 1, the abstract doesn\u2019t actually mention \u2018grinch\u2019 or https:\/\/cov-lineages.org\/global_report.html. It would seem clearer to me to incorporate in the abstract the framing that this article presents a generally applicable software tool, demonstrated on two lineages of concern.<\/i>  Our abstract and introduction now both contain reference to grinch and the reports at cov-lineages.org  \n<i>I would like to see some mention of related efforts somewhere in the report. A full detailed comparison is neither warranted nor useful here because all such websites can and should change regularly, but a couple of sentences comparing cov-lineages.org to sites like outbreak.info and covariants.org would be very useful. At a minimum, it seems useful to list the similar sites the authors are aware of, if only because the fact one can see similar patterns presented on those sites serves as a useful validation of the software presented in this paper.<\/i>  We have added in a short paragraph about these resources and a link to a more extensive (but definitely non-exhaustive) list of resources.  \n<i>Given the situation, this is a desirable, not a requirement, but I\u2019d love to see some unit tests on the GitHub repo. It seems potentially important to have this when the intention is to produce daily updates for public health. (Though I note that getting the same end result from completely independent implementations on other sites is probably worth more than a lot of unit tests).<\/i>  Since publication, we\u2019ve re-worked the back-end analysis pipeline and the GISAID data is now processed with the datapipe pipeline written by Rachel Colquhoun (https:\/\/github.com\/COG-UK\/datapipe). The reports and webpages are still generated with grinch, however the main data processing steps are now done with the robust datapipe pipeline.  \n<i>It\u2019s stated that there is no correlation between the numbers of sequences and flight numbers. It would be nice to see the scatter plot for this (maybe as an inset to figure 1D?), as well as the effect size and p-value of a suitable model. Following from the previous point, the explanation for the lack of a correlation with absolute numbers seems reasonable. But it still seems to me that flight numbers could correlate with the frequency of B117 at a fixed time interval from the first detected case in a given locality (thus somewhat factoring out sequencing effort in the locality). Is it possible to add this analysis?<\/i>  We have amended to state there is no clear relationship, rather than correlation.  \n<i>Please add installation instructions to the GitHub repo.<\/i>  We have added updated usage and install instructions, and a description of the behaviour to the repository, at https:\/\/github.com\/cov-lineages\/grinch\/blob\/main\/README.md  \n<b>Minor comments on https:\/\/cov-lineages.org\/global_report.html:<\/b>  \n<b>Figure 3 for each lineage is a map of sequence counts by region. I find the legend here completely baffling. All it states is grey=No variant (that makes sense), pink = 1 sequence (that makes sense too), and purple = \u2018Max sequences\u2019. I have no idea what to make of this. How many is \u2018Max\u2019, and how am I supposed to quantitatively interpret intermediate colours to pink and purple? It\u2019s so obvious I\u2019m certain there are good reasons why this isn\u2019t already done, but it does seem like a continuous colour scale is what should be used here. Similar to the scale in Figure 2 (grey for no data, shades of green nicely spaced and annotated for different values of a continuous variable).<\/b>  We have since amended the legend for the report.&nbsp; &nbsp; \n<b>For the widespread lineages like B.1.1.7, there\u2019s a lot of overplotting on Figures 4 and 5, which make the counts and the country names very difficult to read. This could be addressed by just making the figures larger.<\/b>  We have made these figures larger, but recognise that these plots may be better displayed by having a top 20 country barchart (like in https:\/\/cov-lineages.org\/lineage.html?lineage=B.1.1.7) and intend to adopt an interactive, more attractive global report in the future. &nbsp; \n<b>The table of links to news reports is absolutely wonderful. Would it be possible to include a button here to allow users to suggest additional news links? (I assume there\u2019s an existing mechanism for doing this, but I couldn\u2019t find one, so if not maybe just a link to a github issue with (potentially) a pre-filled title and required information would help?)<\/b>  \n<b>&nbsp; &nbsp; &nbsp; &nbsp; &nbsp; <\/b>We really like this idea and will work towards implementing it!","URL":"https:\/\/wellcomeopenresearch.org\/articles\/6-121\/v2#referee-comment-4741","order":1,"name":"referee-comment-4741","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.18372.r43964, Anderson F. Brito, Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA, 03 Jun 2021, version 1, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/6-121\/v1#referee-response-43964","order":2,"name":"referee-response-43964","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>&Aacute;ine Niamh O'Toole<\/b>; \n<i>Posted: 10 Sep 2021<\/i>;  \n<b>In the manuscript, the authors mention that users with access to GISAID direct download could run this pipeline locally, and generate their own reports. Can this tool be adapted to display genomic results for tracking national spread, or even state-level spread of lineages?<\/b> We\u2019ve added in an option to grinch with the --analysis flag, that can either run the whole GISAID-processing pipeline, or just generate a set of reports from a metadata file. It currently would need resolution to remain at the country level, but we like the idea of doing a more local report and will work towards implementing something like this in the future.&nbsp; &nbsp; \n<b>If this pipeline is intended to be constantly executed locally by users, it would be helpful to provide more information about how to install and run the pipeline, including reference to example input and output files.&nbsp; I have tried to run the pipeline using my GISAID data provision credentials, but that was not successful, as I ran into errors for which I could not find a solution online (GitHub and Zenodo).<\/b> We have supplied some more information on how to install on the GitHub repository and run the pipeline, however the tool isn\u2019t necessarily intended for users to run locally themselves as we process the data on this end and share the macro count data on GitHub. &nbsp; \n<b>About the online reports, increasing the font size in the plots being displayed (bar, curves, etc) would make labels and legends more intelligible, and improving the readability of their content.<\/b> We have made the axes longer to account for&nbsp;more countries, however are working towards re-implementing these reports in javascript so they can be interactive and more responsive to the browser size.&nbsp; &nbsp; \n<b>About the flight data, why only flight counts from October are shown? Are these data only used for tracking the potential spread in early stages of viral emergence, or do you see other uses for such data?<\/b> October related to the date of early spread of both lineages described in the text and was due to limitations of access to data. We hope to continue to develop this resource and supply more recent dates that track over time.&nbsp;  \n<b>&nbsp;<\/b> \n<b>Concerning the manuscript, a few minor points:<\/b>  \n<b>The colour gradient in the legend of Figure 1 is incomplete and does not go from 1 to 76. I think it must be just a formatting issue.<\/b> This was a proofs issue and we\u2019ve hopefully rectified this now. &nbsp; \n<b>How was the &quot;reported&quot; cases shown in Figures 1 and 2 detected? By differential PCR? I know that applies to B.1.1.7, but what about B.1.351?<\/b> This was the set of manually curated media reports that we were tracking at the time. &nbsp; \n<b>The legend in Figure 2 refers to &quot;B.1.1.7&quot; sequences, while the figure shows &quot;B.1.351&quot; sequences. It must be a typo.<\/b> Thank you we have now fixed this in the figure.","URL":"https:\/\/wellcomeopenresearch.org\/articles\/6-121\/v2#referee-comment-4742","order":3,"name":"referee-comment-4742","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>&Aacute;ine Niamh O'Toole<\/b>; \n<i>Posted: 10 Sep 2021<\/i>; Also- thank you for your time reviewing this manuscript (we do really appreciate it!) and apologies for taking so long to respond.","URL":"https:\/\/wellcomeopenresearch.org\/articles\/6-121\/v2#referee-comment-4744","order":4,"name":"referee-comment-4744","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.18372.r43967, George Githinji, Epidemiology and Demography Department, Kenya Medical Research Institute (KEMRI) - Wellcome Trust Research Programme, Kilifi, Kenya, 10 Jun 2021, version 1, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/6-121\/v1#referee-response-43967","order":5,"name":"referee-response-43967","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>&Aacute;ine Niamh O'Toole<\/b>; \n<i>Posted: 10 Sep 2021<\/i>; Thank you for your review and time, and apologies for taking so long to respond!  \n<b>The transition from an article of public health importance to a software tool is abrupt. I think a paragraph or a link aimed at orientating the audience would be useful.<\/b> We have added in a paragraph that bridges the public health information and the resource information.&nbsp;  \n<b>It would be useful to outline the special niche that the tool occupies or the gaps it fills relative to similar utilities and webpages such as covariants.org and outbreak.info.<\/b> The linking paragraph also discusses other resources such as outbreak.info and covariants.org- we now also provide a non-exhaustive list of a several other resources on the cov-lineages.org website&nbsp;&nbsp; \u200b\u200b\u200b\u200b\u200b\u200b\u200b \n<b>The readme file at https:\/\/github.com\/cov-lineages\/grinch lacks full installation documentation. An introductory paragraph of the tool and its utility would also be useful. The scripts directory could be better organised by separating the snakemake files from the regular python files. I would image a workflows dir and scripts dir<\/b> We have updated the readme on the grinch repository and updated usage in that it can be run in full analysis pipeline mode or in report only mode. We have also added in a brief description of the grinch setup and where the macro data is hosted.\n<b> <\/b>","URL":"https:\/\/wellcomeopenresearch.org\/articles\/6-121\/v2#referee-comment-4743","order":6,"name":"referee-comment-4743","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"I.I.B. is supported by the Canadian Institutes of Health Research, COVID-19 Rapid Research Funding Opportunity (02179-000). K.K. is the founder of BlueDot, a social enterprise that develops digital technologies for public health. K.K., A.W., A.T.B. and C.H. are employed at BlueDot. I.I.B. has consulted for BlueDot. T.d.O. and the NGS-SA is funded by the South African Medical Research Council (SAMRC), MRC SHIP and the Department of Science and Innovation (DSI) of South Africa. N.R.F.\nacknowledges support from a Wellcome Trust and Royal Society Sir Henry Dale Fellowship (204311\/Z\/16\/Z) and a Medical Research Council-S\u00e3o Paulo Research Foundation CADDE partnership award (MR\/S0195\/1 and FAPESP 18\/14389-0). VH was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) [grant number BB\/M010996\/1]. M.U.G.K. acknowledges support from the Branco Weiss Fellowship and EU grant 874850 MOOD. The contents of this publication are the sole responsibility of the authors and do not necessarily reflect the views of the European Commission.\nO.G.P. , J.P.M. and M.U.G.K. acknowledge support from the Oxford Martin School. AR acknowledges the support of the Wellcome Trust (Collaborators Award 206298\/Z\/17\/Z \u2013 ARTIC network) and the European Research Council (grant agreement no. 725422 \u2013 ReservoirDOCS). A.OT is supported by the Wellcome Trust Hosts, Pathogens & Global Health Programme [grant number: grant.203783\/Z\/16\/Z] and Fast Grants [award number: 2236]. COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) and Genome Research Limited, operating as the Wellcome Sanger Institute.TFS acknowledges support from the Deutsche Forschungsgemeinschaft (SFB900, EXC2155 RESIST). SeqCOVID-SPAIN is supported by a grant from the Instituto de Salud Carlos III COV0020\/00140.","order":7,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}