JerMa88/TPR_Peer_Reviews huggingface dataset:
Peer review of: Fossils from Mille-Logya, Afar, Ethiopia, elucidate the link between Pliocene environmental (2020)

Reviewers' Comments:
 Reviewer #1:
 Remarks to the Author:
 I think the revisions have improved the document, and it is ready to be published.
 Reviewer #2:
 Remarks to the Author:
 The revised version of the manuscript is much improved. There are just a few relatively minor
 comments that I think the authors can deal with easily.
1. The authors state that the BL and MD dimensions of MLP-1549 overlap with those of early Homo
and are closest to their mean values. However, from the figures provided, it appears that they overlap
in values with every hominin except for P. robustus. The authors seem to use this as part of their
rationale for identifying the molar as early Homo even though the morphology they provide further
down the paragraph is actually more convincing. It is merely a shift in emphasis I think.
 2. Figure 3 - I would strongly advise the authors to make e. and f. easier to read. Please write out
 taxonomic names instead of labeling them with letters. Larger graphs would be very useful too. These
 are almost impossible to read.
 3. In the discussions of implications of Mille-Logya fauna and paleoenvironment, the authors gloss
 over or do not even mention Ledi-Geraru, which is a significant oversight as it has the oldest known
 Homo specimen and provides important context for the authors' hypothesis of early Homo habitat and
 origin.
4. In supplementary figures 10 and 11, robustus is labeled as both A. and P., please be consistent.
Peer review of: A mechanistic explanation of the transition to simple multicellularity in fungi (2020)



REVIEWERS' COMMENTS: 

Reviewer #1 (Remarks to the Author): 

The authors have done a thorough job in addressing my concerns. In my opinion the manuscript is 
ready for publication. 

Reviewer #2 (Remarks to the Author): 

The authors have satisfactorily addressed all of my comments.
Peer review of: Wild primates copy higher-ranked individuals in a social transmission experiment (2020)


 

Reviewers' Comments: 
 
Reviewer #2: 
Remarks to the Author: 
Thanks for the authors for trying to clarify what they did. Figures S2 and S3 helped me to identify 
where the misunderstanding between the authors and me may have been rooted. Inspecting Fig. S2 
and S3 indicate that the model predicts the likelihood for each subject that it will learn, that is, the 
sample size is correspondingly larger. In other words, the model appears to be predictive in the sense 
that it assigns learning probabilities to different subjects, updating after each event the learning 
probability. This is very different from an approach that starts with the learning event and then 
retrospectively reconstructs what the input was and whether this is in line with CO or OS learning 
(which is what I had assumed, resulting in an N of 14). If I am correct with this diagnosis, the authors 
might want to clarify this in the manuscript. 
 
The predicted values shown in these supplementary figures show that the probability of learning is 
substantially higher when the animals already know one technique; is this the basis for the conclusion 
that these animals learn the new technique individually 31 times faster? If this is the case, the authors 
may want to write that the likelihood to learn is 31 times higher. ‘Faster’ may be misleading here, as 
the model is not based on actual temporal measurements. The details about who touched what when 
can then be moved to the SI, as it does not really appear to be relevant. 
 
Figures S2 and S3: the red line needs to go; lines between points should only used for repeated 
measurements. 
 
I strongly recommend to present Figures S2 and S3 (at least for the best social model) in the main 
part of the manuscript.
Peer review of: Recent hybrids recapitulate ancient hybrid outcomes (2019)


REVIEWERS' COMMENTS: 

Reviewer #1 (Remarks to the Author): 

The authors have addressed all of my comments. I am glad I could help catch an error in the site 
labeling on the PCA. That error was what I found most confusing about the manuscript and the 
interpterion of the JH ancestry (and why I asked for the IBD analyses). The manuscript is definitely 
clearer, and authors did an excellent job of answering my questions. In my opinion, the terms ‘hybrid 
lineages’ and ‘hybrid populations’ suggest they are the outcome of hybrid speciation. But I would 
interpret JH as isolated L. idas populations that have experienced introgression in the past (rather 
than hybrid lineages). Regardless, these terms are not a sticking point for me and I appreciate the 
authors’ perspective. 

When reading the IBD section of the supplement, I noticed two typos: 
First paragraph: “barrier top gene flow” should be “barrier to gene flow”. 
First paragraph, 2nd page: “distance along” should be “distance alone” 

Reviewer #2 (Remarks to the Author): 

The authors have done an admirable job in attending to my concerns. This involved adding several 
additional analyses, which I think have improved this already impressive paper. I have no further 
concerns, except for the tiniest of corrections: please check the labels on figures 3C and 6H. 

-Simon Martin 

Reviewer #3 (Remarks to the Author): 

I have no further comments.
Peer review of: The Seminavis robusta genome provides insights into the evolutionary adaptations of (2020)



 

REVIEWERS' COMMENTS: 

Reviewer #2 (Remarks to the Author): 

My concerns were adequately addressed with this revision. Regarding the quality of the assembly, I 
would suggest that the limitations pointed by the authors should be detailed in the Methods section. 
There are probably ways to improve HMW DNA extraction for diatoms (and to perform HiC), so writing 
about the problems explicitely may help in the future. 

Reviewer #3 (Remarks to the Author): 

I have reviewed the revised version of the manuscript and am satisfied by the author modifications in 
response to my original review.
Peer review of: Comprehensive identification of mRNA isoforms reveals the diversity of neural cell-surface (2020)

Reviewers' comments:
Reviewer #3 (Remarks to the Author):
All my concerns have been adequately addressed. The manuscript is ready for publication.
Reviewer #4 (Remarks to the Author):
The manuscript submitted by Ray et al. describes a strategy to identify full-length isoforms encoded by individual genes. They show the applicability of their strategy by revealing novel unannotated isoforms expressed in retina and brain. One of their key findings is the discovery of a novel CRB1 isoform, which was previously overlooked. A mutant mouse model subsequently suggested that this isoform is related to accelerated photoreceptor death.
With regard to the validation by mass spectrometry:
1) It is not clear to me how big the protein database is which was used for the discovery of novel peptides and whether it contained all potentially present proteins. Despite the enrichment for cell surface proteins, the samples could still be contaminated with other (e.g. intra-cellular) proteins. In order avoid matching fragmentation spectra to known peptides from canonical proteins (in contrast to modified peptides from the same database), the authors should redo their analysis using the Sqanti- generated fasta + UniProtKB mouse fasta.
The authors have tried to do this by searching their data with7 common protein modifications activated. However, it is not clear to me which database was used for this search (Sqanti or full UniProt). In either case, allowing 7 variable modifications increases the search space quite drastically and increases the odds of random matches, subsequently given true positive hits less chance of surviving the FDR cutoff. It is not entirely unexpected that “no potential false identifications were found” by that. Were there any alternative matches to spectra being identified as novel peptides with higher search engines scores in comparison to the unmodified search?
2) The authors have chosen a relatively high peptide level FDR of 5%. How many novel peptides would have survived at an FDR cutoff of 1%? How does the score distribution of novel peptides compare to known peptides? Do they follow the same trend? In the same direction, what is the spectral quality (e.g. S/N, number of peaks) of the spectra identified to be novel peptides vs known peptides?
3) Despite the theoretical validation and given the relatively low number of peptides/spectra to investigate, have the authors considered doing a validation by a) synthetic peptides, b) predicted spectra or c) manual identification? To allow manual investigation, the authors could use tools such as xiSPEC to share annotated spectra of the novel peptides.
Peer review of: A single-cell atlas of the human substantia nigra reveals cell-specific pathways associated (2020)



REVIEWERS' COMMENTS: 

Reviewer #3 (Remarks to the Author): 

The authors have done a good job of responding to the referees' comments 

Reviewer #4 (Remarks to the Author): 

The authors have sufficiently addressed all my concerns, and I recommend the manuscript for 
publication in Nature Communications.
Peer review of: CRISPR GUARD protects off-target sites from Cas9 nuclease activity using short guide RNAs (2020)


Reviewers' Comments: 
 
Reviewer #1: 
Remarks to the Author: 
The authors have addressed all my concerns. I find the paper suitable for publication. 
 
Congratulations on the interesting work! 
 
 
 
Reviewer #2: 
Remarks to the Author: 
Overall, the authors revised and improved the manuscript significantly. The following minor points 
may improve the manuscript further. 
 
 
 
How did the authors design NT GUARDs for all experiments? Their sequences should be described 
in the supplementary tables. 
 
 
 
In all plots, authors should not use statistical tests when ‘n’ is less than three. 
 
 
 
(Line 167) This reviewer does not think that the new high-GC GUARD is superior in this example. 
Previous and new GUARDs gave very small differences (Supplementary figure 4), and the new 
GUARD has a longer overlap with the seed region. Thus, it is hard to say that GC content is the 
only reason for different results. Based on supplementary figure 11, GC content should affect the 
GUARD function, but it may not be the case here. The manuscript needs to be revised accordingly. 
 
 
 
(Supplementary figure 6b) The legend is referring figure 1a, but probably it is figure 1. Even 
though readers may be able to understand the directionality of the sequence, the convention is to 
match (left to right) to (5′ to 3′). In the figure, however, some are with 5′ to 3′ and others with 3′ 
to 5′. The directionality should be indicated clearly. 
 
 
 
(Figure 4b and c) When comparing two plots for MFAP1 GUARD, the rate of off-target editing 
coming from GUARD is much higher when GUARD is delivered with on-target gRNA. Is there any 
explanation for this? 
 
 
 
(Figure 6f) ‘High GC content of > 50%’ may not be included here or modified because data at 
supplementary figure 11a does not support the cut-off of 50%. From the data, GC content higher 
than ~35% seems more appropriate. 
 
 
 
(Line 321) Supplementary table 4 is not present. 
 

 
 
(Figure 2) It is written in the legend that figure 2a is showing mean ± SD from two experiments, 
and 2b from three experiments. However, 2a seems to show the result from a single experiment, 
and 2b is a schematic. These errors should be corrected.
Peer review of: Targeting QKI-7 in vivo restores endothelial cell function in diabetes (2020)


 

Reviewers' Comments: 
 
Reviewer #2: 
Remarks to the Author: 
I do not have any additional question 
 
 
 
Reviewer #3: 
Remarks to the Author: 
The RIPs look good and now provide direct evidence for binding to the transcript
Peer review of: Targeting QKI-7 in vivo restores endothelial cell function in diabetes (2020)

 

 

Reviewers' Comments: 
 
Reviewer #1: 
Remarks to the Author: 
I have no additional comments/questions. 
 
 
 
Reviewer #2: 
Remarks to the Author: 
The manuscript is substantially improved, but the study of angiogenesis is still not complete and 
questionable. In Figure 7D the authors used HE to count capillaries. They report values of 
capillaries that are very low compared with the expected cap in the murine muscle (5 to 7 
hundreds caps/mm2). Is the number reported 5 to 10 cap/mm2 this would be low even for 
arterioles. 
 
Moreover this figure refers only to the analysis of the exp with silencing but not to the one with 
iPS. Both need to be assessed. In doing so, they should use a specific marker for endothelial cells 
and SMCs such as CD31/lectin and aSMA respectively. Then use morphometry. 
 
Moreover, the authors did not performed the suggestion to study proliferation and apoptosis, 
therefore it is not clear from where the change in vascularity derives. 
 
 
 
Reviewer #3: 
Remarks to the Author: 
 
 
I asked for evidence of physical binding of the RBP to the QKI-7 transcriptt. Other than 
identfication of potential binding sites this was not provided. Ergo this remains speculative 
 
minor: 
 
In bottom abstract grammer make e.g. "QKI-7 was knocked down... 
 
Also the rebuttal says experiments are now performed with 4 different ips-EC but fig S6 and 7 only 
refer to HD22 and PO23 did I look at the revised figures? 

Targeting QKI-7 in vivo Restores Endothelial Cell Function in Diabetes
Peer review of: Detecting sample swaps in diverse NGS data types using linkage disequilibrium (2020)


REVIEWERS' COMMENTS: 

Reviewer #1 (Remarks to the Author): 

The authors successfully address most of my previous concerns. I appreciate the authors’ efforts. I 
think the manuscript is now publishable. I only have a few minor questions and comments 
regarding this revision. 
1. In the comparison with other tools, I agree with the authors that HYSIS and Bam-matcher are 
difficult to apply. For BamixChecker, however, users can provide BED files to specify the target 
sites. I wonder if the authors applied all the appropriate parameters for the comparison. 
2. I found that the familial dataset has been mapped to hg38, but the authors mentioned that all 
settings were based on hg19. 

Reviewer #2 (Remarks to the Author): 

The authors have addressed all of my comments and have come out with interesting analysis 
addressing familial relatedness and sample swapping that were not included in the original 
manuscript which have enhanced the paper and made its point much stronger. I believe the paper 
merits publication.
Peer review of: The mutREAD method detects mutational signatures from low quantities of cancer DNA (2020)

 

REVIEWERS' COMMENTS: 

Reviewer #1 (Remarks to the Author): 

Overall, the authors addressed the main concerns and significantly improved the manuscript. I have 
only a couple of minor points to mention: 

1) It is satisfactory that the signatures and cosine similarities were comparable to the previous 
observations, after including Strelka as an alternative variant caller. However, there still seems an 
issue that merits more discussion, and that is the effects of the individual callers on the obtained 
mutation counts and on their overlap. Specifically, the FF MutREAD consensus (Supp Table 3A) 
represents on average a mere 44% of the MuTect calls (this drop is not observed by WGS), and in 
Supp Table 3C (FFPE mutation counts) there is about the same average drop seen (44%). There might 
not be much to do about these differences and the performance of these specific callers on mutREAD 
data. However, the choice of callers, their performance settings and the effects on the resulting 
mutation counts should be discussed in more depth, simply to raise the awareness of the readers 
about a caveat to be systematically addressed through benchmarking and optimization. 

2) What is now Suppl Table 4 is labeled on the xls sheet Supp Table 3, while the new Supp Table 3 
(the caller comparison) has no sheet labeling within – please check if all referencing of display/data 
items resulting from the revision 

Reviewer #2 (Remarks to the Author): 

The responses to the reviewer's concerns are adequate. No further comments.
Peer review of: Tracing animal genomic evolution with the chromosomal-level assembly of the freshwater (2020)



Reviewers' Comments: 
 
Reviewer #1: 
Remarks to the Author: 
The authors revised to almost all of comments properly. One concern is about the 
revised sentence in abstract (lines 62 - 64). I feel the possible relationship between 
environmental adaptation and duplicated genes could be discussed in the 
manuscript since I cannot find it in the main text. Do 85 orthologroups with 
differential expressions (lines 332 - 334) include large number of lineage-specific 
duplicated genes since a gemmule stage is required for adaptation to extreme 
habitat? 
 
 
 
Reviewer #2: 
Remarks to the Author: 
The authors have done a good job in addressing my queries (as well as those of 
other reviewers). In my opinion the manuscript can be published in Nature 
Communications. 

Kenny et al. Tracing animal genomic evolution with the chromosomal-level assembly of the 
freshwater sponge Ephydatia muelleri
Peer review of: Ethanol exposure increases mutation rate through error-prone polymerases (2020)


 
 

REVIEWERS' COMMENTS: 
 
Reviewer #2 (Remarks to the Author): 
 
The authors have satisfactory responded to my criticism, and I recommend that the manuscript is 
accepted for publication. 
I congratulate the authors on this important contribution to the mechanistic insight on the 
mutagenesis and potentially carcinogenesis caused by ethanol. 
Zvi Livneh
Peer review of: Ethanol exposure increases mutation rate through error-prone polymerases (2020)


 

 

Reviewers' comments: 
 
Reviewer #1 (Remarks to the Author): 
 
The authors have addressed my concerns and have improved the manuscript. I really enjoyed this 
thought-provoking study. 
 
 
Reviewer #2 (Remarks to the Author): 
 
The authors have made an effort to address the concerns raised. However, I am still puzzled by 
the lack of any involvement of acetaldehyde derived adducts in the mutagenesis. Particularly 
puzzling is the lack of effect on mutation frequency upon acetaldehyde treatment, contrary to 
earlier published results. If the lack of effect of acetaldehyde is not a technical problem, it may be 
supporting the author's argument of additional mechanisms for ethanol-induced mutagenesis, 
because it would mean that at least in the strain they studied, ethanol, but not acetaldehyde, 
caused mutations. 
To sort this out, I suggest the following: 
1. The effect of acetaldehyde on mutations should be tested in 2 other yeast strains. If an effect of 
acetaldehyde is found, it can serve as a 'positive control'. It may also indicate that the effect they 
originally observed is strain specific, but it may still be generally relevant. 
2. If at least one of the strains in item 1 shows increased mutations, the combined action of 
ethanol plus acetaldehyde should be tested. Are they additive? The two may react to form an 
acetal, but it would be important to test it in any case. 
3. The authors argue that they did not find in the CAN1 ORF a GG-to-TT mutation, typical of 
acetaldehyde-induced mutations. Thy should check whether this type of tandem double mutation, 
if formed, can generate a canavanine-resistant mutation. It might not be possible 
4. Experiments 1 and 2 cshould be repeated also with another mutagenesis assay system (URA3? 
Other?) 
If this point is sorted out, the manuscript will be acceptable.
Peer review of: GWAS of thyroid stimulating hormone highlights pleiotropic effects and inverse association (2009)



REVIEWERS' COMMENTS: 

Reviewer #1 (Remarks to the Author): 

I would like to thank the Authors for fully addressing all issues and explaining the points that were 
unclear to me. 

Reviewer #2 (Remarks to the Author): 

The authors have satisfactorily responded to the questions of the reviewers and made the 
necessary changes to the manuscript. 

Minor comment: 
There is a discordance between the number of cases and controls indicated in the text ("3,359 
thyroid cancer cases and 694,949 controls") and in the Supp Table 11 ("1,361 cases and 686,390 
controls") for thyroid cancer analysis using DeCode and UKB. Also p-values for heterogeneity and 
direction of effects are missing in the table. 

Reviewer #3 (Remarks to the Author): 

The authors have adequately addressed my concerns. I have only couple of minor points below: 

I agree with the authors that the LDSC regression approach was not developed for mixed models. 
However, several studies have successfully used this approach on the GWAS summary statistics 
obtained from linear mixed models to investigate inflation of the test statistics due to relatedness 
or population structure. For example, please see Lou et al, Nat Genet 2018 
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6309610/) which uses attenuation ratio defined 
as (LDSC intercept – 1)/(mean χ2 – 1) for the summary statistics obtained from linear mixed 
model in Bolt LMM. However, because the author have shown that the linearity assumption in the 
LDSC regression approach does not hold for their TSH GWAS, I agree that it will not be 
appropriate to use LDSC regression for their study. 

Thanks for including r2 estimates for the PGS analyses. I noticed that the authors have specified 
that “We also evaluated the phenotypic variance (r2 on the liability scale) explained by TSH PGS…”. 
As age, sex, and PCs were also included as covariates in the PGS analyses, the r2 should refer to 
the variance explained by all these variables collectively? Or was r2 estimated for the PGS variable 
alone? If the former, I suggest re-phrasing the sentence to show that the r2 estimates are for the 
full model. 

For the DEPICT tissue enrichment analysis, still none of the tissues show significant results after 
correction for multiple testing (P<0.05/208 tests) or FDR<0.05. I think when the authors talk 
about the top tissues in the manuscript (e.g. tissues from the digestive system, etc.), it worth 
reminding the readers that none of these tissues passes the significance threshold.
Peer review of: Accounting for diverse evolutionary forces reveals mosaic patterns of selection on human (2020)



Reviewers' Comments: 
 
Reviewer #1: 
Remarks to the Author: 
The authors have satisfactorily addressed by concerns, I have no further comments. 
 
 
 
Reviewer #2: 
Remarks to the Author: 
Authors revised the manuscript on evolutionary analyses on preterm birth. Regrettably, this author 
found that the comments were not addressed. 
 
1. It must be necessary to apply the set of the revolutionary analyses to much wider ranges of the 
phenotypes, rather than only applying to preterm birth. This reviewer concerns that assessing only 
one phenotype could induce biased conclusion, as well as lack of contribution to human phenotype-
genotype studies. 
 
2. Number of the samples, especially those in whole-genome sequencing, is small to make any robust 
conclusions. Authors can put more efforts to access much wider ranges of the data, most of which are 
publicly available. 
 
 
 
Reviewer #3: 
Remarks to the Author: 
After reading the authors's responses, I still disagree with them on the specific point that their method 
is immune to the same issues as the outlier approach. If you think about it, the tested locus could still 
be by chance an outlier compared to the matched control loci, even if there is no selection. The only 
way to know then that there is an actual signal is through enrichment analysis. The approach taken by 
the authors arguably decreases the issues of the outlier approach by limiting them to specific genes, 
but it is not entirely solving these issues. This should not prevent publication though because the 
enrichment analysis conducted by the authors is now much more convincing that actual interesting 
selection patterns have taken place. I have no further concern about the manuscript.