Description

The aim of this review is to describe challenges and opportunities for analysis of big health data (BHD). It describes 5 areas: "Structured vs unstructured BHD", "Graph Networks", "Classification", "Incompleteness", "Exploratory Data Analytics", "Predictive analytics", "Services and Infrastructure" and "Data Harmonization and Fusion". In each of the sections, different methods, issues and infrastructure are mentioned. The paper does not compare the method, give guidelines for when to use which method or come with any testable scientific claims. Therefore, the paper can be viewed as a catalog of methods used within BHD analysis. The added value or novelty of this review is that it might be the first review listing all these methods.

Major Issues

The number of methods listed is overwhelmingly large, and their descriptions lack in depth discussion and comparison. Listing so many methods does not give the reader an overview. There is only in few cases where strengths and weaknesses of methods are discussed (e.g. PCA versus ICA). It would add great value to this review if usage, advantages and disadvantages were discussed in depth for a smaller number of methods rather than the naming of a large catalog of methods. Citing 166 articles does to me seem like excessive use of citations.

The introduction (the first non-captioned section) does not define a scope for the review (like "In this review, we will…"). It also does not state a gap of knowledge that the review fills. Although these things can be found in the abstract, it would be nice to have them explicitly stated in the introduction. Perhaps, the introduction could also get a caption?

Although the review mentions an extensive number of papers, it does not mention network medicine in the "Graph Networks" section or cite any of Albert-László Barabási's influential work in this field. Though network medicine can be viewed as more relevant to analysis of protein-protein interaction and other molecular data, there are several BHD methods analyzing patient record data. For example CA Hidalgo, N Blumm, A-L Barabási, NA Christakis, A dynamic network approach for the study of human phenotypes., PLoS Comput. Biol. 5 (2009), doi:10.1371/journal.pcbi.1000353 or Albert-László Barabási, Natali Gulbahce & Joseph Loscalzo, Network medicine: a network-based approach to human disease. Nature Reviews Genetics 12, 56-68 2011, doi:10.1038/nrg2918.. It would be relevant for the topic to discuss some of this topic.

Minor Issues

The illustrations in Figure 1 and Figure 5 do not add any information that could not be displayed in a table. The spokes-wheels (Figure 3) and the human body -> brain -> etc. pictures (Figure 5) does not illustrate any point.

In Figure 5, the highlighted lungs on the human body (left) "emits" a blue cloud pointing at the brain. This does not make any sense.

In Figure 1, the scaling of text size with the size of the spokes-wheels renders the smallest text hard to read.

In the "Exploratory Data Analytics" section (p. 8 line 38), the comparison of words and pictures is a bit cryptic. Rather than describing the saying, the section ought to address the issue of illustrations versus text descriptions directly.

Citation numbering seems to start in the figures. In the main text, the first citation number is [5]. This might not be on purpose.

Conclusionn

Since there are no scientific claims, tests, comparisons or in this review, there is nothing scientifically that could be wrong. The list of methods is very comprehensive and covers much of a data analytics standard tool kit. However, since there is only little in-depth discussion of methods, the review does not add much value. The review would benefit from being focused on a smaller number of methods and to span a smaller number of areas.

Generally, the language is of high grammatical correctness and is easy to understand.

Level of interest

Please indicate how interesting you found the manuscript:

An article of limited interest

Quality of written English
Please indicate the quality of language in the manuscript:
Acceptable

Declaration of competing interests
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1. Have you in the past five years received reimbursements, fees, funding, or salary from
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5. Do you have any other financial competing interests?

6. Do you have any non-financial competing interests in relation to this paper?

If you can answer no to all of the above, write 'I declare that I have no competing interests'
below. If your reply is yes to any, please give details below.

I declare that I have no competing interests.

I agree to the open peer review policy of the journal. I understand that my name will be included
on my report to the authors and, if the manuscript is accepted for publication, my named report
including any attachments I upload will be posted on the website along with the authors'
responses. I agree for my report to be made available under an Open Access Creative Commons
CC-BY license (http://creativecommons.org/licenses/by/4.0/). I understand that any comments
which I do not wish to be included in my named report can be included as confidential comments
to the editors, which will not be published.

I agree to the open peer review policy of the journal.

The reviewed version of the manuscript can be seen here:

All revised versions are also available:

All my minor points have been addressed. I am still convinced that the review lacks focus and mentions to many things rather than describing them better; and that it should be revised. However, if the editor is comfortable with the current scope, I have found no other issues that should be addressed before publications.

Level of interest
Please indicate how interesting you found the manuscript:
An article of limited interest

Quality of written English
Please indicate the quality of language in the manuscript:

Acceptable

Declaration of competing interests
Please complete a declaration of competing interests, considering the following questions:

1. Have you in the past five years received reimbursements, fees, funding, or salary from
an organisation that may in any way gain or lose financially from the publication of this
manuscript, either now or in the future?

2. Do you hold any stocks or shares in an organisation that may in any way gain or lose
financially from the publication of this manuscript, either now or in the future?

3. Do you hold or are you currently applying for any patents relating to the content of the
manuscript?
4. Have you received reimbursements, fees, funding, or salary from an organization that
holds or has applied for patents relating to the content of the manuscript?

5. Do you have any other financial competing interests?

6. Do you have any non-financial competing interests in relation to this paper?

If you can answer no to all of the above, write 'I declare that I have no competing interests'
below. If your reply is yes to any, please give details below.

I declare that I have no competing interests.

I agree to the open peer review policy of the journal. I understand that my name will be included on my report to the authors and, if the manuscript is accepted for publication, my named report including any attachments I upload will be posted on the website along with the authors' responses. I agree for my report to be made available under an Open Access Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0/). I understand that any comments which I do not wish to be included in my named report can be included as confidential comments to the editors, which will not be published.

I agree to the open peer review policy of the journal.

Authors' response to reviews: (http://www.gigasciencejournal.com/imedia/2073544102008157_comment.pdf)