Title: Changes in the salivary metabolome in patients with chronic erosive gastritis
Version: 2 Date: 21 Oct 2022
Reviewer's report:
The manuscript by Liu et al. entitled: ”Changes of salivary metabolomics in patients with
chronic erosive gastritis” describes the application of RP and HILIC-LC-MS based untargeted
metabolomics to study metabolic signature of CEG disease. In my opinion, besides the effort
made by Authors, the manuscript should not be accepted for publication in the current version.
The major issues that should be considered before manuscript resubmission have been listed
below:
1. The main drawback of this study is a lack of proper metabolite identification. The metabolite
identification is based only on searching through HMDB database. This is only putative
identification only based on monoisotopic masses. At least MS/MS fragmentation spectra should
be provided according to Metabolomics Standards Initiative (MSI) criteria. Without at least
such confirmation of metabolite identities is not possible to make any proper biochemical
interpretation and conclusions of the study.
2. In the manuscript the term metabonomics has appeared mainly in the discussion section.
Please clarify it, because based on the tittle and methodology described in the manuscript, the
metabolomics approach was applied. These definitions are not the same.
3. Please describe more details about procedure used for saliva samples preparation, especially
the volume of reagents and sample used. There is an information: “take an appropriate amount
of sample, add precooled methanol / acetonitrile / aqueous solution (2:2:1, V / V)…”. It is not
useful to repeat the procedure in other studies.
4. Have any other normalization strategy been tested for the raw data?
5. For calculation of p-value the multiple testing for p-value correction should be applied, such
as FDR procedure.
6. For PCA plots there is a lack of explanation of CT-CEG and CT-N groups
7. In the Table with metabolite annotation data please provide which were detected by RP and
HILIC mode, respectively. It will be worthy to include also measured mass, RT, fragmentation
spectra, ionization mode for each potential metabolite.
8. There are many language errors in the manuscript. The text of the manuscript should be
inspected, corrected  and revised before resubmission.
Title: Changes in the salivary metabolome in patients with chronic erosive gastritis
Version: 2 Date: 21 Oct 2022
Reviewer's report:
The manuscript by Liu et al. entitled: ”Changes of salivary metabolomics in patients with
chronic erosive gastritis” describes the application of RP and HILIC-LC-MS based untargeted
metabolomics to study metabolic signature of CEG disease. In my opinion, besides the effort
made by Authors, the manuscript should not be accepted for publication in the current version.
The major issues that should be considered before manuscript resubmission have been listed
below:
1. The main drawback of this study is a lack of proper metabolite identification. The metabolite
identification is based only on searching through HMDB database. This is only putative
identification only based on monoisotopic masses. At least MS/MS fragmentation spectra should
be provided according to Metabolomics Standards Initiative (MSI) criteria. Without at least
such confirmation of metabolite identities is not possible to make any proper biochemical
interpretation and conclusions of the study.
2. In the manuscript the term metabonomics has appeared mainly in the discussion section.
Please clarify it, because based on the tittle and methodology described in the manuscript, the
metabolomics approach was applied. These definitions are not the same.
3. Please describe more details about procedure used for saliva samples preparation, especially
the volume of reagents and sample used. There is an information: “take an appropriate amount
of sample, add precooled methanol / acetonitrile / aqueous solution (2:2:1, V / V)…”. It is not
useful to repeat the procedure in other studies.
4. Have any other normalization strategy been tested for the raw data?
5. For calculation of p-value the multiple testing for p-value correction should be applied, such
as FDR procedure.
6. For PCA plots there is a lack of explanation of CT-CEG and CT-N groups
7. In the Table with metabolite annotation data please provide which were detected by RP and
HILIC mode, respectively. It will be worthy to include also measured mass, RT, fragmentation
spectra, ionization mode for each potential metabolite.
8. There are many language errors in the manuscript. The text of the manuscript should be
inspected, corrected  and revised before resubmission.
Please review this paper.
user
Title: Changes in the salivary metabolome in patients with chronic erosive gastritis
Version: 2 Date: 21 Oct 2022
Reviewer's report:
The manuscript by Liu et al. entitled: ”Changes of salivary metabolomics in patients with
chronic erosive gastritis” describes the application of RP and HILIC-LC-MS based untargeted
metabolomics to study metabolic signature of CEG disease. In my opinion, besides the effort
made by Authors, the manuscript should not be accepted for publication in the current version.
The major issues that should be considered before manuscript resubmission have been listed
below:
1. The main drawback of this study is a lack of proper metabolite identification. The metabolite
identification is based only on searching through HMDB database. This is only putative
identification only based on monoisotopic masses. At least MS/MS fragmentation spectra should
be provided according to Metabolomics Standards Initiative (MSI) criteria. Without at least
such confirmation of metabolite identities is not possible to make any proper biochemical
interpretation and conclusions of the study.
2. In the manuscript the term metabonomics has appeared mainly in the discussion section.
Please clarify it, because based on the tittle and methodology described in the manuscript, the
metabolomics approach was applied. These definitions are not the same.
3. Please describe more details about procedure used for saliva samples preparation, especially
the volume of reagents and sample used. There is an information: “take an appropriate amount
of sample, add precooled methanol / acetonitrile / aqueous solution (2:2:1, V / V)…”. It is not
useful to repeat the procedure in other studies.
4. Have any other normalization strategy been tested for the raw data?
5. For calculation of p-value the multiple testing for p-value correction should be applied, such
as FDR procedure.
6. For PCA plots there is a lack of explanation of CT-CEG and CT-N groups
7. In the Table with metabolite annotation data please provide which were detected by RP and
HILIC mode, respectively. It will be worthy to include also measured mass, RT, fragmentation
spectra, ionization mode for each potential metabolite.
8. There are many language errors in the manuscript. The text of the manuscript should be
inspected, corrected  and revised before resubmission.
assistant