Whole Genome DNA Methylation Analysis of Active Pulmonary Tuberculosis Disease Identifies Novel Epigenotypes: PARP9/miR-505/RASGRP4/GNG12 Gene Methylation and Clinical Phenotypes
, Chang-Chun Hsiao 1,2, Ting-Wen Chen 3,4,5,6, Chao-Chien Wu 1, Tung-Ying Chao 1, Sum-Yee Leung 1, Hock-Liew Eng 7, Chiu-Ping Lee 1, Ting-Ya Wang 1 and Meng-Chih Lin 1,*Round 1
Reviewer 1 Report
I totally agree on your approach with DNA methylation patterns to the development of active pulmonary TB.
Moreover it's very important to remember , as you done in abstract , the number of infectious disesases that TB kills in the word every year .
Very interesting and best compliments and to increase in human knowledge, susceptibility to active TB disease, and of course, always like in your paper , the regulation of human immunologic responses that passes by memory immunity to Mtb persistence and by dissemination by DNA methylation levels of genes in P.B.M.Cs on a genome -wide scale.
Also innovative in my opinion as described in table 1 and in particular demografic and clinical characteristics in the sputum positive pulmonary TB patiens and healthy subjects in the discovery and validation cohorts .
While very important in the paper evolution identification of PARP9 to promote interferon stimulation and regulation macrophage activation.
As well as I like role and study of FOX03 that can reverse of inibitory effect of miR -223 on macrophage apoptosis.
In a general contexts very articulated and well outlined I ask you at least a short conclusion, that would be right see in a job of this importance , quality and relevance.
Author Response
Response to Reviewer 1
I totally agree on your approach with DNA methylation patterns to the development of active pulmonary TB.
Moreover it's very important to remember , as you done in abstract , the number of infectious disesases that TB kills in the word every year .
Very interesting and best compliments and to increase in human knowledge, susceptibility to active TB disease, and of course, always like in your paper , the regulation of human immunologic responses that passes by memory immunity to Mtb persistence and by dissemination by DNA methylation levels of genes in P.B.M.Cs on a genome -wide scale.
Also innovative in my opinion as described in table 1 and in particular demografic and clinical characteristics in the sputum positive pulmonary TB patiens and healthy subjects in the discovery and validation cohorts .
While very important in the paper evolution identification of PARP9 to promote interferon stimulation and regulation macrophage activation.
As well as I like role and study of FOX03 that can reverse of inibitory effect of miR -223 on macrophage apoptosis.
In a general contexts very articulated and well outlined I ask you at least a short conclusion, that would be right see in a job of this importance , quality and relevance.
Ans.: As suggest, we add a paragraph of conclusions after the discussion section.
Reviewer 2 Report
The manuscript needs checking for minor errors and some errors are marked in the attached PDF file.
Comments for author File: 
Comments.pdf
Author Response
Response to Reviewer 2
The manuscript needs checking for minor errors and some errors are marked in the attached PDF file.
Ans.: As suggest, we correct the minor errors.
