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Reviewer response for version 1
Structure
The authors provide an analysis of HA sequences of recent H3N2 influenza viruses from the ongoing season using the protein sequence-based clustering algorithm ISTREE.
Recap
This method has been developed and published by one of the authors several years ago.
Recap
ISTREE seeks to combine molecular data and provide a clustering with respect to antigenic relatedness of the influenza virus HA.
Recap
Previous publications provided a retrospective analysis of genetic and antigenic data.
Other
Basically, ISTREE is advertised as an alternative to antigenic cartography of influenza viruses using serologic data based on hemagglutination inhibition (HI).
Recap
In fact, such algorithms would be of great interest and value in terms of vaccine selection.
Strength
The prospective statements re appropriate vaccine strains for a future influenza season made by the authors here are quite clear but they are solely based on ISTREE assessments.
Recap
No flanking/supporting data based on standard HI assays is provided.
Weakness
Assessing the validity of the ISTREE data therefore is not possible.
Weakness
The data may well turn out to be useful but, as it currently stands, they may be totally misleading as well.
Weakness
Solid antigenic data will be required to validate the potentially useful ISTREE algorithm.
Todo
Reviewer response for version 1
Structure
Below my considerations.
Structure
I believe that the article can be indexed with minor adjustments.
Other
I do not agree with the statement: "In the last decades, Brazil has faced different arbovirus epidemics. However, none of them had the complexity of Zika virus and associated diseases".
Weakness
Dengue has caused and still causes serious public health and has much higher mortality rate in Brazil.
Other
The article cites many epidemiological bulletin of the Ministry of Health.
Recap
This is important, but it has some articles that deserve to be mentioned.
Todo
As an example, we have published papers citing cases of zika in Brazil (RN and BA) before the publication of the Ministry of Health report.
Other
Even with all the advances cited by the authors I believe that it is necessary to mention the delay in the release of funds for research on zika in Brazil.
Todo
Reviewer response for version 1
Structure
The article 'Thousands of exon skipping events differentiate among splicing patterns in sixteen human tissues' presents a systematic analysis of alternative splicing of the Illumina Body Map RNA-seq set, probably the most complete set of RNA-seq data to date.
Recap
This data set consists of 160M reads each for 16 tissues, each from a different individual.
Recap
From the standpoint of a reviewer I consider this article to be of very good quality, and have very much enjoyed reviewing it.
Strength
There are a few suggestions I hope could help improve this work.
Structure
- P3. pp.2:
Structure
Has alternative splicing profiling been attempted before?
Todo
If so, could this please be shown in the background section?
Todo
If not, how does this technique specifically differ from what has been done before?
Todo
Some more context would be appreciated.
Todo
- P3. pp.3:
Structure
What is the effect of comparing tissues from 16 different individuals?
Todo
I would expect that the genetic variation of each individual would have some effects in the actual AS patterns observed when compared.
Other
I see that these samples belong to people with different ethnic backgrounds and ages.
Recap
I would be interested to know what the authors think about how different results would be if all 16 tissues had been from one individual.
Todo
- I tried to compile ASprofile on a mac and I got this error:
Weakness
libc.h:15:20: error: malloc.h: No such file or directory I solved this by changing this line with #include <stdlib.h>.
Other
Perhaps you might want to add these lines, so that mac users do not encounter the problem:
Todo
#if !defined(__APPLE__) #include <malloc.h> #endif
Other
- Although the license for ASprofile is available in the Zenodo page, it might also be a good idea to mention it somewhere in the article.
Todo
Not mentioning a license may make some users uneasy, even if it says it is open source.
Weakness
- In S1, how many of the mapped reads were properly paired?
Todo
- Why did you use such old versions of Ensembl genes (Ensembl 61, February 2011), UCSC Genes, CCDS genes and H-DBAs?
Todo
I also find that the TopHat (v1.3.3) and Cufflinks (v0.9.3) versions are quite old.
Weakness
The current version for TopHat is 2.0.9 and the current version for Cufflinks is 2.1.1.
Other
The current version of Ensembl is version 73, September 2013.
Other
The usage of such old versions concerns me a little, particularly those of the gene annotations, given that a lot of the results that are presented in this work rely heavily on the comparison of AS profiles against those annotations.
Weakness
Some of the results might be different if a newer version of the annotations were up-to-date.
Weakness
- P5. pp.5:
Structure
The example of a novel event in CHTOP does not provide clear evidence as to how many reads support the novel exon.
Weakness
Please provide some numbers.
Todo
- P7. pp1:
Structure
Please could you provide evidence for the novel putative intron retention event located in the chr7:123269489-123270019 region?
Todo
- In Figure S7.B, I would appreciate some text describing the biological significance of having the 100 bin in the x-axis with the greatest bars.
Todo
Overall I am unable to understand what this figure means.
Weakness
Reviewer response for version 1
Structure
Well written paper on an important and largely ignored subject: ‘health workers perspectives for guidelines’;
Strength
Also on top global health issue ‘Ebola virus disease’.
Recap
Study process was speedy and appropriate for the urgency needed for guidelines to be developed making this a good learning experience.
Strength
However, there are a few points of attention listed below.
Other
I have also highlighted the sections relevant to my comments here .
Other
Methods
Structure
AQ1:
Structure
‘The 2014–2016 EVD outbreak in West Africa was initially declared a Public Health Emergency of International Concern in early August 2014, coinciding with the decision to develop a WHO rapid advice guideline on the selection and use of PPE for EVD care in outbreaks.’
Recap
This statement will fit more within the background section, consider moving into background.
Todo
AQ2:
Structure
‘We electronically surveyed international frontline physicians and nurses who participated in foreign medical teams deployed to the affected countries in early stages of the EVD outbreak.’
Recap
Clearly stating time frame in the methods section within which survey was done will also be helpful for readers, although a time frame is given later under participants, it is not clear if this was for survey or the sampling.
Todo
this time frame is also very early in the outbreak
Recap
AQ3:
Structure
Settings is not well described, consider discussing setting in more detail under a separate title.
Todo
Results
Structure
AQ4:
Structure
Clinicians express discomfort and safety, it may be interesting to know if at some point in the interviews they weighed in on safety versus comfort e.g. will the feeling of safety make them cope with discomfort?
Todo
Or does discomfort make safety inconsequential?
Other
Reviewer response for version 1
Structure
I had difficulty reading the tables in the article.
Weakness
I thought maybe it was the way they were displaying on my computer, but nothing seemed to change when I clicked on them.
Other
Please make these charts simple to read and clear.
Todo
I need to see the tables to make sure your findings are adequately described.
Other
The article is really well written.
Strength
I was very pleased with the quality of the writing and the honesty of the authors about their challenges.
Strength
This is important work in the area of PPE use.
Strength
While I know that this was quick work in a difficulty setting, I still feel like the article needs to do justice to personal protective equipment research of the past 20 years (at least since SARS).
Todo
The major section that needs more referencing is the discussion section.
Todo
How do your findings compare to what we have found in epidemiological studies, simulation studies, and others on PPE.
Todo
Even if these studies were not done in the context of an outbreak of EVD in Africa, they should still be discussed.
Todo
There is literature on some of these areas that would bring worthwhile context to your findings.
Other
Reviewer response for version 1
Structure
The author presents a R based toolset for the analysis of ChIP-seq data in a GUI framework.
Recap
The construction of R based ChIP-seq analysis pipelines affords the potential for the use of wide range of tools from R and Bioconductor libraries while offering a low dependency piece of software.
Recap
ChIPdig uses QuasR, a wrapper for Bowtie, for the alignment of ChIP-seq data from a BSGenome object.
Recap
The Rbowtie2 and Rsubread packages are now both available on Windows, Mac and Linux systems and should be considered alongside Bowtie.
Todo
I believe they would offer significant speed and memory usage improvements over QuasR. Although these do not accept BSGenome objects, ChIPdig could easily generate the FASTA from these packages for use with indexing steps of both packages.
Other
Blacklisted regions should be considered in this tool as they have been shown to have strong effects on the QC, fragment length estimation and between sample normalisation.
Todo
Inclusion of methods of blacklist filtering from known sources (such as Encode) or in software derived blacklists (using GreyListChIP) should be performed.
Todo
The output of BedGraph instead of BigWigs may cause some problems for users when working with larger genomes such as human or mouse.
Weakness
BigWigs may not be able to be exported on Windows systems but users of Mac or linux should have this option available to them to make this feature worthwhile.
Other
Peak calling is performed with BayesPeak.
Recap

This data is made available as part of the work Revise and Resubmit (https://doi.org/10.1162/coli_a_00455). Specifically, I have processed prag.csv from the project Github page (https://github.com/UKPLab/f1000rd) to be easily used for sentence classification using HuggingFace models. The sentences from the datasets are split into train/dev/test using the original splits.csv file from the Github repo.

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