Content of review 1, reviewed on July 28, 2014

GWATCH is an innovative and well-conceived idea, successfully implemented and presented as a web-platform. Such tools are necessary and timely at present in order to tackle the burgeoning data in genomics. GWATCH can prove to be useful, especially in light of their applications in genomic-studies like genome-wide association studies (GWAS). New GWAS studies based on next-generation-sequencing (NGS) data, at-present taking place simultaneously across different parts of the world, will require such online-tools, in order to quickly compare, analyse and replicate genomic-association results.

To this end, the innovative visualization tools developed through GWATCH, and the detailed results for every SNP for different studies, can prove to be very useful for researchers. The manuscript is well written and the online tutorial and the content of the web-site is simple, but useful and easy to follow. However, in order to publish this work in accordance with the intended content and purpose of GWATCH.

I would like to advise the following corrections and modifications.

  1. The manuscript mentions GWATCH can do association and visualization of indels and copy number variants (CNVs), but there are no examples for these. Visualization of copy-number classes, breakpoints along with the SNP data might be useful for researchers, hence an example how to do this can be added to the GWATCH documentation.

  2. It might be useful if the GWATCH results and web-pages can show the genomic-build of the datasets being displayed. Further, allowing the users to convert from one build to another can prove to be useful. The past, present and the future build-coordinates are likely to change, hence this is an important issue to be addressed. This feature might also be added to the search fields for genomic co-ordinates.

  3. The Active-Datasets tab on the GWATCH web-portal has long names for the various datasets stored, but no identifiers (ids) specific to GWATCH database. Adding an identifier might be more useful for users for searching and comparing results in future.

  4. The authors state that GWATCH can be applicable to sequencing based GWAS as well, but there is no documentation in the manuscript or online, regarding how to upload sequencing results or in which format they should be used. In case the authors want the users to convert sequencing results into the GWATCH specific format, then some guidelines and instructions might be provided. If the authors wish to mention sequencing capability of GWATCH in the manuscript, they must show some examples or details of how to use sequencing data for GWATCH.

  5. The GWATCH database should also allow some general data-mining tools which require less prior knowledge from the users. For example, at present it seems that a one can search by gene-name, only if user first selects the correct chromosome. There is no genome-wide tool for searching by gene-names or SNP ids. This might pose a bit of inconvenience and can be easily rectified.

  6. On the website, there seems to be no way of registering new users. There is only login for existing users. The authors might want to add further documentation and details regarding how to do this.

  7. The highway-browser is a and novel useful tool for visualizing association results. However, some improvements may added such as, allowing the users to choose colours (especially for colour-blind people). Further, an option to add a filter for p-value thresholds may help in visually plotting interesting results on the highway-browser and further remove background-noise.

  8. The TRAX report does not mention the genotyping-platform and also the genomic-build for the reported SNP. These details can be added.

  9. The authors mention the calculation of principal components analysis and meta-analysis for their example AIDS datasets. It is not clear from the manuscript whether this functionality are intended to be a part of the GWATCH platform or is for the user to do it. Also the authors can include details whether and how covariates can be added to the association model in the GWATCH.

  10. GWAS-central is a similar online tool available at present. The authors can perhaps highlight some of the advantages and differences of using GWATCH over GWAS central, and highlight instances where it can prove to be more useful for a researcher. The authors may also want to list the current limitations of GWATCH and their planned future work, mainly related to how they want to develop this in future and tackle the future challenges.

  11. The authors might want to clarify more regarding the open source license for this project.

Tisham De and Lachlan Coin

Level of interest:

An article of importance in its field

Quality of written English:

Acceptable

Statistical review:

Yes, and I have assessed the statistics in my report.

Declaration of competing interests:

No

Source

    © 2014 the Reviewer (CC BY 3.0 - source).

References

    Anton, S., Sergey, M., Nikolay, C., Paul, G., Mikhail, R., Pavel, D., Andrey, S., Li, G., Jennifer, T., Sher, H., Hutcheson, D. H., K., O. T., Sharyne, D., Edward, G., A., J. D., Efe, S., Mark, V. N., Richard, H. P., L., B. Z., J., O. S. 2014. GWATCH: a web platform for automated gene association discovery analysis. GigaScience.