JerMa88/TPR_Peer_Reviews huggingface dataset:
Peer review of: ucleoplasmic signals promote directed transmembrane protein import simultaneously via (2020)



REVIEWERS' COMMENTS: 
 
Reviewer #1 (Remarks to the Author): 
 
The authors addressed satisfactorily my previously raised concerns, and therefore recommend to 
accept the manuscript for publication in Nature Communications. 
 
 
Reviewer #2 (Remarks to the Author): 
 
My concerns have been dealt with satisfactory and I support publication. I have one remaining 
suggestions: 
 
To show the complete western in S13 and not just a section reflecting where the full length protein 
runs, as this control is meant to take away the concern of (soluble) breakdown products complicating 
the interpretation of the data.
Peer review of: Lipid-protein interactions modulate the conformational equilibrium of a potassium channel (2020)

REVIEWERS' COMMENTS: 
 
Reviewer #1 (Remarks to the Author): 
 
All questions are answered satisfactory. I have no further comment and therefore recommend this 
paper to be published in Nature Communications. 
 
 
Reviewer #2 (Remarks to the Author): 
 
In the revised manuscript the authors addressed to all reviewer comments, and I can recommend 
the paper for publication 
 
 
Reviewer #3 (Remarks to the Author): 
 
I am satisfied with all changes made to the manuscript. Congratulations on an excellent study.
Peer review of: A machine learning-based chemoproteomic approach to identify drug targets and binding (2020)


 

Reviewers' Comments: 
 
Reviewer #2: 
Remarks to the Author: 
In this work, Piazza and Beaton et al. improve their previous limited proteolysis approach to identify 
targets of small molecules in cell lysates. Compared to previous studies, the authors used a dose-
response approach that allows the use of a more stringent statistical method. I had previously 
reviewed this manuscript for another journal and most of my comments have been addressed. This 
has significantly improved the manuscript, but there are still some points that I think the authors need 
to address. 
1. The authors should address the limitations of their intact cell experiment, since limited proteolysis 
needs to be performed after lysis (even if the treatment is performed in living cells). The authors 
should include in the discussion that the lysis procedure can lead to reequilibration of compound 
binding and protein-protein interactions. This can lead to the compound no longer preventing 
proteolysis of some proteins, or the compound being able to access proteins that were not available 
before (e.g., due to subcellular compartmentalization) – leading to possible false negatives and 
positives. 
2. While I appreciate that the authors now cite more recent and sensitive chemical biology 
approaches, the comparison of their method to these is still not entirely fair. 
a. First, only one replicate from the Savitski 2014 dataset was used. It is clear from the publication 
from which this dataset was retrieved that in this mode of TPP (TPP-TR), at least two replicates of 
each condition should be used. 
b. Second, the authors did not properly annotate the TPP dataset, probably due to problems matching 
IPI access numbers to Uniprot IDs – a quick look reveals that the third hit and some hits further down 
(LIMK2, STK4 and STK11) are not annotated as kinases despite being present in kinhub.org (and the 
authors Table S6). This leads to these proteins being annotated as false positives. 
c. This led me to repeat the benchmark, by using the same datasets (Savitski 2014, LiP-Quant and 
Deep-LiP_Quant), but with a more sensitive way of calling hits that was used to analyze this 
staurosporine TPP dataset and published last year (Childs et al. Mol. Cell. Prot. 2019) and carefully 
annotating all the datasets. I attach a markdown file of this analysis that I am happy that the authors 
use directly in their manuscript. This highlights that, as pointed out in my first comments, LiP (and 
also Deep-LiP) has lower coverage than other chemical biology approaches and is therefore less 
sensitive. There is no need for the authors to try to hide that LiP-Quant is less sensitive than other 
approaches, since it has other strengths, such as the ability to pinpoint the binding site of the 
compound.
Peer review of: Widespread protein lysine acetylation in gut microbiome and its alterations in patients with (2020)



Reviewers' Comments: 
 
Reviewer #1: 
Remarks to the Author: 
The authors have addressed the critiques raised. 
 
 
 
Reviewer #2: 
Remarks to the Author: 
In general, the authors have done a careful and diligent job in considering and responding to the 
various review comments. This included some new work to address concerns, along with very 
detailed comments of new text/figures added. While not perfect, the revisions reflect most of the 
major comments of the three reviewers - as such, this manuscript is greatly improved in terms of 
both content and clarity. 
 
I have only two remaining concerns: 
 
1. P.2, top - the authors' statements of CD in the Abstract are still too over-reaching. In response 
to reviewer comments, they have now toned down the tenor in the manuscript, but this abstract 
needs to be revised to soften the results of the relatively few CD samples, which bring up some 
issues of general conclusions. 
 
2. p. 10, lines 295-302 - the addition of the temporal variability (or lack thereof) of the protein 
acetylation is good, but this occurs too late in the manuscript, and in fact too late even in the CD 
discussion. The reader will want to know this information far earlier in the text - the authors 
should see how they can either move this section or allude to the key message much earlier. This 
would give the reader some assurance that the acetylation variability is not stoichastic. 
 
 
 
Reviewer #3: 
Remarks to the Author: 
The authors have addressed the concerns raised. They have attempted to showcase the value of 
this resource by better describing which proteins are being modified and providing at least one 
example of structural mapping. This could have been extended but it already gives others an idea 
that there will be many examples of novel regulatory acetylation sites potentially found in these 
data. The authors also improved other aspects of the paper and are more cautious about the 
messages that can be derived from a relative small cohort size. I have not further concerns.
Peer review of: A scalable CRISPR/Cas9-based fluorescent reporter assay to study DNA double-strand break (2020)



REVIEWER COMMENTS 
 

 
Reviewer #1 (Remarks to the Author): 
 
The authors have addressed most of my comments. 
 
 

 
Reviewer #2 (Remarks to the Author): 
 
The manuscript has improved significantly and the authors have addressed a significant fraction of 
the queries. However, I still have the following issues. 
 
1. The authors have presumably sorted the mCherry+/GFP- and mCherry-/GFP- populations and 
directly measured the distributions of the lengths of breaks in each sub-population using Illumina 
and Oxford Nanopore platforms. However, the authors do not explicitly state what populations 
were used for the sequencing neither in the main text nor the Methods part. They only use word 
“sorted” in the Figure 1 and Supplementary Figure 1 and therefore it is not exactly clear what was 
done. This analysis is at the core of validation of their high-throughput assay. As such, it should be 
emphasized and described in much more detail in the main text and methods. It would be also 
good to see a panel in a main figure that shows exact gating parameters used in this sorting-
sequencing experiment. 
 
2. In terms of the inducible Cas9 cell lines, the authors state that they cannot detect Cas9 
expression without Doxycycline induction, while they still observe the unwanted DSBs events in 
the absence of induction and claim that those are due to the leakiness of the inducible promoters. 
I think the authors should provide more evidence to support this conclusion, and/or they should 
provide a more detailed clarification of the observed results. Furthermore, the Cas9-mediated site-
specific DNA cleavage is at the core of their method and the authors should show that the increase 
in the breaks and increase in the fraction of the mCherry+/GFP- and mCherry-/GFP- populations is 
Dox-dependent. 
 
3. The authors now include estimates of the statistical significance, however, they only use them 
in the context of yes or no answers as to the significance of their observations. The readers might 
want to look at the actual values to make their own determination about relative significance of 
various treatments. Therefore, I think the author should make a Supplementary Dataset with the 
actual p-values and %-ages for every sorted fraction for every drug treatment and gene knockout 
(eg, ATM, PARP etc) tested in this work. 
 
4. The authors provide 3 supplementary tables, but they only mention one of them in the text. 
 
 
 
Reviewer #3 (Remarks to the Author): 
 
The authors have adequately addressed my critiques.
Peer review of: High throughput error corrected Nanopore single cell transcriptome sequencing (2019)


 

Reviewers' Comments: 
 
Reviewer #1: 
Remarks to the Author: 
The authors have addressed my concerns on the description of the transcript novelty. It was nice to 
see that novel transcripts are detected at least by 2 cells. 
 
However, I would strongly suggest they use SQANTI categories to describe the novelty as this is the 
standard in the field and most of their definitions of novel transcript classes correspond to an already 
defined SQANTI category. 
 
The authors should be sure none of the novel transcripts have non-canonical splice sites. I do not 
expect this to be a major problem because of the 2 cells filter, but just in case.
Peer review of: A rare variant of African ancestry activates 8q24 lncRNA hub by modulating cancer (2020)


 
 

REVIEWERS' COMMENTS: 
 
Reviewer #1 (Remarks to the Author): 
 
The authors have addressed my questions. 
 
 
Reviewer #3 (Reviewer Replacement to comment on behalf of Reviewer #2, Remarks to the 
Author): 
 
The authors have provided thorough responses to the reviewer comments.
Peer review of: Engineering AvidCARs for combinatorial antigen recognition and reversible control of CAR (2020)


9 

Reviewers' Comments: 
 
Reviewer #1: 
Remarks to the Author: 
Thank you - the authors have addressed my comments to my satisfaction. Very nice work. 
 
 
 
Reviewer #2: 
Remarks to the Author: 
All the issues and concerns are addressed properly. I have no any further questions.
Peer review of: OSMR controls glioma stem cell respiration and confers resistance of glioblastoma to (2020)



Reviewers' Comments: 
 
Reviewer #1: 
Remarks to the Author: 
My concerns have been sufficiently expressed. 
signed: Christel Herold-Mende 
 
 
 
Reviewer #2: 
Remarks to the Author: 
The revised paper has been much improved showing the localization of OSMR in mitochondria of 
different cellular types. However, this reviewer does not find mechanistic explanation, or 
sufficiently convincing arguments, to explain the OSMR-mediated activation of mitochondrial 
respiration. Likewise, there is no mechanistic explanation to address the inhibition of the activities 
of the four respiratory complexes studied when OSMR is silenced.
Peer review of: Genomic characterization of malignant progression in neoplastic pancreatic cysts (2020)


REVIEWERS' COMMENTS: 

 

 

Reviewer#1: 

the authors addressed all my concerns adequately. 

 

Reviewer#2: 

I appreciate the extensive comments made by the authors made on exactly delineating why this 
study demonstrates novelty compared to prior data. Also the clarification on ATM is accepted.
Peer review of: Pancreatic cancers suppress negative feedback of glucose transport to reprogram chromatin (2020)



Reviewers' Comments: 
 
Reviewer #3: 
Remarks to the Author: 
The authors sufficiently addressed my concerns. 
 
 
 
Reviewer #4: 
Remarks to the Author: 
The authors have answered most of the questions raised during the first course of reviewing. The manuscript has 
improved. No more comments.
Peer review of: FGF2 alters macrophage polarization, tumour immunity and growth and can be targeted (2020)



Reviewers' Comments: 
 
Reviewer #1: 
Remarks to the Author: 
Overall, the authors have incorporated many changes and the manuscript has been improved. One 
concern is regarding the experiments provided in response to the suggestion to demonstrate that 
FGF2 directly activates FGFR signaling in TAMs. The authors have provided data in Supplemental 
Figure 3 in which they treated macrophages with recombinant FGF2 and examined expression of 
inflammatory genes. They also treated cells with tumor cell conditioned medium followed by an 
FGF2 antibody. It is not clear whether appropriate controls were included. The source of 
recombinant FGF2 was not found. BMDMs are highly sensitive to even low levels of endotoxin, 
commonly found in most recombinant protein preparations, which can impact expression of 
inflammatory genes. In addition, it does not appear that an isotype control antibody was used in 
the antibody blocking experiments. Therefore, these data are difficult to interpret and do not 
provide convincing evidence for direct regulation of macrophage polarization by FGF2 via FGFR 
signaling. 
 
There is also concern regarding the experiment provided in Supplemental Figure 7C. These 
experiments are ideally performed following serum starvation for short timepoints (5-30 minutes). 
Given the transient nature of FGF2-induced signaling it is unclear that analysis of signaling 
pathways 48 hours after treatment (in an undefined serum setting) provides 
meaningful/interpretable information. Furthermore, an appropriate positive control should also be 
included (such as a cell known known to respond to FGF2 stimulation). While it is agreed that 
FGFR phosphorylation can be difficult to detect, phosphorylation of FRS-2 is generally considered 
to be a relevant surrogate and is more specific than Akt and ERK. 
 
 
 
Reviewer #3: 
Remarks to the Author: 
The Authors have provided adequate responses and revisions after the first round of reviews 
 
 
 
Reviewer #5: 
Remarks to the Author: 
This is an interesting and clearly written paper. this reviewer has been asked to comment on 
whether the issues raised by reviewer 4 have been adequately addressed. 
 
In the most part, the comments from reviewer 4 have been addressed. However for point 3 the 
authors couldnt get the antibodies to work, and the autocrine pathway requested was not possible 
to provide. 
 
Point 5 was responded to by 'beyond the scope of this study', which is a little disappointing but 
probably does change the message of the paper 
 
Reviewer 4 point 7 - for angiogenic responses an n=3 is not sufficient for statistical analysis and 
this n-number should be increased 
 
The point abput regrowing escape cells in FGF2lmw-/- was not done. Again this is a shame, 
because although it may not change the paper it would have been of interest.
Peer review of: ABL1-dependent OTULIN phosphorylation promotes genotoxic Wnt/β-catenin activation to (2020)



Reviewers' Comments: 
 
Reviewer #1: 
Remarks to the Author: 
The authors have addressed most of the major concerns raised by the reviewers. The paper is now 
appropriate for publication. 
 
 
 
Reviewer #2: 
Remarks to the Author: 
According to our criticisms, the authors dramatically improved the manuscript. The findings are 
novel and the experiments are carefully done. Although I am almost satisfied with the authors’ 
responses, I would like to ask one question again. As already commented in (1) and (4), the 
authors should show direct results indicating whether or not the state of M1-ubiquitination of β-
catenin is affected by Wnt3a stimulation. The authors suggested that LUBAC-promoted linear 
ubiquitination has independent but collaborative roles of GSK3-dependent phosphorylation of β-
catenin in controlling its stability. If Wnt simulation directly affects linear ubiquitination of β-
catenin, it would give a strong impact on the Wnt research field.
Peer review of: ABL1-dependent OTULIN phosphorylation promotes genotoxic Wnt/β-catenin activation to (2020)


 

Reviewers' Comments: 
 
Reviewer #2: 
Remarks to the Author: 
The new data supports the important finding that Wnt reduces linear ubiquitination of β-catenin, 
thereby controlling Wnt signaling. This reviewer has no further question.
Peer review of: The REGγ inhibitor NIP30 increases sensitivity to chemotherapy in p53-deficient tumor cells (2020)


 

REVIEWERS' COMMENTS: 

Reviewer #1 (Remarks to the Author): 

This manuscript has been revised in response to my previous comments. Some responses are 
satisfactory, but others, in my opinion, remain unsatisfactory. I continue to believe that 
acknowledgment of earlier work (ref 32) is inadequate with respect to the findings therein and 
their relationship to data in the current manuscript (e.g. insight to and identification of the 
phosphorylation sites, effects of phosphorylation, etc, etc). I also consider the description, conduct 
and analysis of the in vitro degradation experiment I questioned previously to be inadequate - 
including weight-amounts of some proteins is a bare minimum of new information. Finally, 
although somewhat improved, the presentation still includes a number of odd word choices and 
syntax throughout and there many typos and inappropriate formatting, especially in the Reference 
section.
Peer review of: MGMT genomic rearrangements contribute to chemotherapy resistance in gliomas (2020)

	

REVIEWERS' COMMENTS: 
 
Reviewer #1 (Remarks to the Author): 
 
I have no further issues with this manuscript. I commend the authors on a job well done. 
 
 
Reviewer #2 (Remarks to the Author): 
 
my previous concerns have been adequately addressed
Peer review of: European polygenic risk score for prediction of breast cancer shows similar performance in (2015)


 
 
 

REVIEWERS' COMMENTS:

Reviewer #2 (Remarks to the Author):

The authors have addressed my comments adequately

Reviewer #3 (Remarks to the Author):

The authors have made a comprehensive response to the questions raised by the reviewers. The 
addition of explanatory comments and re-editing has improved the clarity of the paper and there 
are no significant revisions that I would suggest.

Appreciating that the paper has been well reviewed and revised there were a couple of points that 
might be addressed for the final text:

Line 297 - the two figures here seem to be for Asians in Asia and Asians in America but it is not 
actually clear and could be spelled out

Line 414 - it may be worth noting that this figure (20%) would then be around the same as it is in 
the European population - as written it leaves the impression that this is still exceptional

Line 441 - "the PRS based on large European-ancestry studies may be used as the basis for Asian-
specific breast cancer risk prediction models" - although it has been well covered in the text this 
summary statement probably still needs to have a caveat such as "that take into account the 
unique distribution of the PRS in the Asian population" to avoid giving the impression that the risk 
prediction produced by the standard European-trained model (such as generated by BOADICEA or 
from commercial labs) is 'good enough' for the interpretation of genotype data from an Asian 
woman.

Reviewer #4 (Remarks to the Author):

The authors have adequately responded to all queries. One point of confusion that remains is what 
analyses use SNP weights from Europeans vs. SNP weights from Asians and how do these results 
compare. This needs to be better defined in the methods, figure/table legends and in the results 
section.
Peer review of: AXL confers cell migration and invasion by hijacking a PEAK1-regulated focal adhesion (2020)



REVIEWERS' COMMENTS: 

Reviewer #1 (Remarks to the Author): 

The authors have satisfactorily addressed all of the points necessary for publication. 

Reviewer #2 (Remarks to the Author): 

The authors state that now on page 6 that there is minimal phosphatidylserine due to apoptotic 
cells in their assay. Nonetheless, it remains imperative that their Gas6-His be complexed with 
phosphatidylserine in order to activate AXL. Thus, the authors need to explain where the 
phosphatidylserine is coming from in order to account for their Gas6-His mediated AXL 
phosphorylation. 

Reviewer #4 (Remarks to the Author): 

The reviewer appreciates the efforts of the authors. The revised manuscripts with new experiments 
have addressed most of the reviewer’s concerns. Although some caveats remain, including the 
functional relevance of PEAK1 phosphorylation and duplicate analysis of SILAC quantification, this 
reviewer agrees that they are not essential to this study and the major conclusions are supported 
by a large body of evidence. Overall, the work identified an important signaling pathway with 
functional significance in cancer metastasis and it is recommended for publication.
Peer review of: Micro-environmental sensing by bone marrow stroma identifies IL-6 and TGFβ1 as (2020)

REVIEWERS' COMMENTS: 

Reviewer #1 (Remarks to the Author): 

The authors have adequately addressed the comments of all reviewers, and have considerabley 
improved the manuscript. 

Reviewer #2 (Remarks to the Author): 

The authors have satisfactorily addressed my concerns. 

Reviewer #3 (Remarks to the Author): 

In this study, the authors interrogate the basis for the altered hematopoietic stem cell function with 
age. Using a combinatorial approach of probing stromal cells as molecular sensors for cytokine 
signalling, they reveal that both Tgfb and IL6 signalling is altered with age. By a series of functional 
experiments (predominantly by inhibiting the activity of these mitogens) they are able to separate the 
functional effects of these pathways on overall lineage potential and erythropoiesis, respectively. 

The paper has many original lines of experimentation and is likely to be influential in the field. The 
results are clearly presented, the methods are well described, and they have adequately adressed all 
the concerns I raised in connection to my review of their original submitted manuscript.