PONE-D-19-29254

Unraveling the Role of Salt-Sensitive Genes in Obesity with integrated Network Biology and Co-Expression Analysis

PLOS ONE

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ACADEMIC EDITOR: Please improve the quality of the images according to journal guidelines. 

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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5. Review Comments to the Author

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Reviewer #1: The manuscript describes a study by the authors which identifies network of salt sensitivity genes and their co-expressed genes to trace the molecular pathways connected to obesity in visceral adipose tissues using gene expression and weighted protein interaction network. This work systematically outlines an integrated bioinformatics pipeline for figuring out the most indispensable key signatures from the interactome Salt Sensitivity Protein Interaction Network. Most recent bioinformatics tools and software have been employed in this investigation, hence it proves the gene's role or its association to Obesity. Touching upon a burning problem like obesity is a good analysis. The manuscript is interesting and publishable in PLOS one journal after the minor issues are addressed by authors.

1. In the introduction section, the authors have mentioned “We have also adopted another novel concept i.e. gene-gene correlation…….” replace “novel concept” with some other suitable word as the mentioned concept is not novel

2. References needed for “The statistical difference between differentially expressed genes (DEGs) was computed using unpaired t-test measure among healthy and obese samples.”

3. References needed for protein interaction databases mentioned in the section the section 2.3

4. References needed for “Next, the plugin NetworkAnalyzer, calculated the degree centrality betweenness….” Mentioned in the section 3.2

5. In the section “3.5 Co-expression analysis” Eight among the 23 co-expressed genes were not previously reported for the disease obesity via gene ontology analysis. Replace the phrase ‘gene ontology’ with suitable word like functional enrichment or gene set enrichment analysis

6. In the section, 4 Discussion,

“Local parameter DC and global parameter BC were used to dissect the complex interactome.”

The terms Local parameter and global parameter are not given any explanation in method or results section

Reviewer #2: The present study has analyzed the contribution of salt sensitivity genes (SSGs) to adiposity in obese patients. They have used a secondary gene expression data set of visceral adipose tissues for performing gene network and pathway enrichment analysis of salt sensitivity genes. They have shown that SSGs and co-expressed gene partners participate in diverse classes of metabolic pathways like those involving lipid metabolism, adipogenic pathways, renin-angiotensin system regulation, etc.

This is the first study conducted looking at the role of SSGs in adipose tissues. They used diverse systems biology methods gene correlation and topological parameters based on graph theory for expression data to identify biomarkers related adipogenesis.

I believe that their network biology provide will provide a novel association with potential biological comprehensions and support future translational assessment on SSGs and obesity. The introduction of this article provides a brief history of the problem and describes the study rationale, methods are provided in detail (including formulas), results & discussions sections are also presented well.

Overall, this article is well prepared and understandable to readers.

I recommend this study to be published in PLOS One Journal in the present form.

Reviewer #3: I would like to congratulate all the stake holders of the study, for their valuable contribution for trying to find some cues to alleviate obesity from world population. In modern world this is the major problem associated with many diseases.

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Reviewer #1: No

Reviewer #2: Yes: SYED SHOEB IQBAL RAZVI

Reviewer #3: No

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Unraveling the Role of Salt-Sensitivity Genes in Obesity with integrated Network Biology and Co-Expression Analysis

PONE-D-19-29254R1

Dear Dr. Khan,

We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.

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With kind regards,

Narasimha Reddy Parine, Ph.D

Academic Editor

PLOS ONE