Submited on: 18 Jan 2016 05:58:17 AM GMT
Published on: 18 Jan 2016 09:19:26 AM GMT
 
Mucin- like Domain (MLD) Reviewer report.
Posted by Dr. Krishna R Khairnar on 29 Feb 2016 09:32:21 AM GMT Reviewed by Author Invited Reviewers

  • What are the main claims of the paper and how important are they?

    A comparative multi-sequence amino acid analysis of the poorly conserved MLD was performed. With consideration of the homology between all species within GP1 and GP2 and the critical interacting residues within GP1, the residues located within the B-cell E1 epitope (301-316) and three MHC Class II epitopes may be responsible for vascular access to these immune privileged site and persistent symptoms observed in the convalescent PEVDS. These B-cell and T-cell epitopes within the mucin-like domain may ultimately be responsible for clinical findings in PEVDS. 


  • Are these claims novel? If not, please specify papers that weaken the claims to the originality of this one.

    Yes.


  • Are the claims properly placed in the context of the previous literature?

    Yes.


  • Do the results support the claims? If not, what other evidence is required?

    Yes.


  • If a protocol is provided, for example for a randomized controlled trial, are there any important deviations from it? If so, have the authors explained adequately why the deviations occurred?

    No deviations.


  • Is the methodology valid? Does the paper offer enough details of its methodology that its experiments or its analyses could be reproduced?

    Yes.


  • Would any other experiments or additional information improve the paper? How much better would the paper be if this extra work was done, and how difficult would such work be to do, or to provide?

    -


  • Is this paper outstanding in its discipline? (For example, would you like to see this work presented in a seminar at your hospital or university? Do you feel these results need to be incorporated in your next general lecture on the subject?) If yes, what makes it outstanding? If not, why not?

    I feel this work is outstanding in its discipline. The data analysis, on the basis of Ebola virus outbreaks in different regions and result predictions by the use of various bioinformatics tools, makes it excellent. Again the findings of this study are very appreciable and beneficial for further research and welfare of society.


  • Other Comments:

    Comment 1: The manuscript has inappropriate expression without use of commas.

    e.g.: To study these convalescent symptoms in Liberia, in June of 2015, a study was launched following people in Liberia who have survived Ebola virus disease (EVD) within the past two years every 6 months for 5 years called  PREVAIL. (Page no. 3, Introduction section, Para 2, First 5 lines)

     

    Comment 2: The manuscript have too long sentences, it should be clear & easily understandable.

    e.g.: In sentence “To study the mucin-like domain further, a comparative multi sequence amino acid analysis of the poorly conserved MLD was performed and all 16 B-cell epitopes previously identified comparing all virulent species of Ebola virus against RESTV was used to identify regions that could explain the differential virulence and vascular access to regions of immune privileged regions.” Make this sentence simpler (Abstract, Para 2, First 8 lines)

     

    “Within the MHC class I predictions, there did not appear to be a statistically significant difference between the virulent species and RESTV. However, the MHC Class II predicted epitopes did identify a statistically significant difference between the virulent species and RESTV.” It could have been managed in a single sentence also. (Abstract, 3 Para, First 6 lines)

     

    Comment 3: Abstract seems to be too long and discussing conclusions with unclear logic. It should be short and precise.

    e. g.: “This study suggests that the residues located within the B-cell E1 epitope (301-316) and three MHC Class II epitopes may be responsible for vascular access to these immune privileged site and persistent symptoms observed in the convalescent PEVDS.” Why not E5-E8 epitope region of B cell, due to its conserved nature as per previous statement in Abstract? (Abstract, Last or Para 4, First 5 lines)

     

    Comment 4: The abbreviations need to be fully mentioned at the beginning for text followed by use of only abbreviation throughout the text..

    e.g.: RESTV, SUDV, TAFV, and BDBV etc.

     

    Comment 5: “In their study, published in Lancet, Volume 15, No. 8, p905–912, August 2015”. This sentence seems to be inappropriate and incomplete. (Page no. 4 Introduction section, Para 3, lines 11 & 12)

     

    Comment 6: The manuscript has some error in words.

    e.g.: 1. Blast, it should be BLAST, (Page no. 5, Materials and method section, Para 1, line 1)

                  2. MCH-I, it should be MHC-I. (Page no. 6 Table 1, line 1) & (Page no. 11 Discussion section, Para 2, lines 18)

    Comment 7: Support these sentences with reference.

    e.g.: “The Ebola glycoprotein is 676 aa in length and contains GP1, the mucin-like domain (MLD), GP2-delta, and GP2. The GP1 receptor binding region (position 53-201, length 181 aa) contains the critical residues for binding at positions 57, 63, 64, 88, 95, and 170. GP1 is responsible for binding to the receptor(s) on target dendritic and endothelial cells.”

     

    “GP2 (position 502-676) is classified a class I viral fusion..………

    …….. immune surveillance and cell adhesion.” (Page no. 5, Pathogenesis section, Para 2, & 3)

  • Competing interests:
    .
  • Invited by the author to review this article? :
    Yes
  • Have you previously published on this or a similar topic?:
    No
  • References:
    None
  • Experience and credentials in the specific area of science:

    I have relevant work experience and have published my specific works in following journals. J Health PopulNutr; BMC Microbiol; J Gastroenterol; BMC Infect Dis; Clin Infect Dis; BMC Genomics; Malar J etc

  • How to cite:  Khairnar K R.Mucin- like Domain (MLD) Reviewer report.[Review of the article 'The Glycoprotein Mucin-Like Domain (MLD) in the Zaire ebolavirus (EBOV) may be responsible for the manifestations of Post-Ebola Virus Disease Syndrome (PEVDS) ' by Roberts L].WebmedCentral 2016;7(2):WMCRW003274
1 2 3 4 5 6 7 8 9
Report abuse
 

Dear Dr. Khaimar,

Thank you! We have been busy with the Zika outbreak and wanted you to know I'm revising the Ebola article as per your recommendations. If I could be of assistance to you, let me know.

Cheers,

Rick Ricketson


Responded by Dr. Robert Ricketson on 21 Mar 2016 03:56:10 PM

  • What are the main claims of the paper and how important are they?

    The primary claim is that predicted epitopes within the MLD of ebolavirus strains are resposible for manifestation of PEVDS.


  • Are these claims novel? If not, please specify papers that weaken the claims to the originality of this one.

    The link between PEVDS and epitopes seems to be novel, and thus may constitute an important finding if validated properly.


  • Are the claims properly placed in the context of the previous literature?

    Yes


  • Do the results support the claims? If not, what other evidence is required?

    It is possible that the results support the claims, but the description of epitope prediction protocol is not detailed enough to afford confidence.


  • If a protocol is provided, for example for a randomized controlled trial, are there any important deviations from it? If so, have the authors explained adequately why the deviations occurred?

    N/A


  • Is the methodology valid? Does the paper offer enough details of its methodology that its experiments or its analyses could be reproduced?

    The paper provides almost no description of the protocol for epitope prediction (i.e., the scoring criteria for identifying epitope candidates or the empirical model by which epitope binding is estimated).


  • Would any other experiments or additional information improve the paper? How much better would the paper be if this extra work was done, and how difficult would such work be to do, or to provide?

    Must better document methdology before this question can be fully addressed.  If detailed information is given on the epitope prediction methodology and the extent to which the methodology has been successfully validated in past cases, a better assessment will be possible for whether the existing method is adequate.


  • Is this paper outstanding in its discipline? (For example, would you like to see this work presented in a seminar at your hospital or university? Do you feel these results need to be incorporated in your next general lecture on the subject?) If yes, what makes it outstanding? If not, why not?

    Probably not.  The findings may prove important (if suitably validated) but it is unlikely that the analytical method will rise to the level of being particularly innovative or rigorous.


  • Other Comments:

    Numerous grammatical errors, such as:

    A prior study by Yang in 2000 demonstrated the mucin-like domain was responsible for the vascular permeability and inflammation seen in EVD with Zaire ebolavirus infections but not in Reston ebolavirus infections. Demonstrated *that* the mucin-like domain

    To study the mucin-like domain further, a comparative multi-sequence amino acid analysis of the poorly conserved MLD was performed and all 16 B-cell epitopes previously identified comparing all virulent species of Ebolavirus against RESTV was used to identify regions that could explain the differential virulence and vascular access to regions of immune privileged regions.

    Incomprehensible run-on sentence. Grammatical veracity is doubtful.


    The C-terminus GLINT motif in epitope E16 of the MLD at the GP2 junction was

    moderately conserved between all species including RESTV and therefore not felt to contribute to the overall differential virulence and *was* therefore not felt Secondary tertiary structures were obtained as previously described with the final total charges

    assigned to that segment obtained from the PQR output file (Table 6). What is meant by "Secondary tertiary"? To the best of my knowledge, a tertiary structure always attempts to incorporate secondary structure elements by default.

    There was no significantly significance within the MHC Class I epitopes between the virulent and nonvirulent species of Ebolavirus (p=0.067). Significantly significance?


    To evaluate this potential, the binding potential of the MCH I and MHC II was obtained by submitting the amino acid sequence of the mucin-like domain to the IEDB

    database and filtered to those with high binding affinities and *filtering* to those with high binding affinities.

  • Invited by the author to review this article? :
    Yes
  • Have you previously published on this or a similar topic?:
    No
  • References:
    None
  • Experience and credentials in the specific area of science:

    As a researcher with substantial experience in predicting protein structure and function, I so confirm

  • How to cite:  Lushington G H.Review of paper reporting link between epitopes in ebolavirus MLD and PEVDS manifestation[Review of the article 'The Glycoprotein Mucin-Like Domain (MLD) in the Zaire ebolavirus (EBOV) may be responsible for the manifestations of Post-Ebola Virus Disease Syndrome (PEVDS) ' by Roberts L].WebmedCentral 2016;7(2):WMCRW003271
1 2 3 4 5 6 7 8 9
Report abuse