Identification of important modules and biomarkers in tuberculosis based on WGCNA

BackgroundTuberculosis (TB) is a significant public health concern, particularly in China. Long noncoding RNAs (lncRNAs) can provide abundant pathological information regarding etiology and could include candidate biomarkers for diagnosis of TB. However, data regarding lncRNA expression profiles and...

Full description

Bibliographic Details
Main Authors: Jing Dong, Ruixue Song, Xuetian Shang, Yingchao Wang, Qiuyue Liu, Zhiguo Zhang, Hongyan Jia, Mailing Huang, Chuanzhi Zhu, Qi Sun, Boping Du, Aiying Xing, Zihui Li, Lanyue Zhang, Liping Pan, Zongde Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-02-01
Series:Frontiers in Microbiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmicb.2024.1354190/full
_version_ 1797320631547592704
author Jing Dong
Jing Dong
Jing Dong
Ruixue Song
Ruixue Song
Ruixue Song
Xuetian Shang
Xuetian Shang
Xuetian Shang
Yingchao Wang
Yingchao Wang
Yingchao Wang
Qiuyue Liu
Qiuyue Liu
Zhiguo Zhang
Hongyan Jia
Hongyan Jia
Hongyan Jia
Mailing Huang
Mailing Huang
Chuanzhi Zhu
Chuanzhi Zhu
Chuanzhi Zhu
Qi Sun
Qi Sun
Qi Sun
Boping Du
Boping Du
Boping Du
Aiying Xing
Aiying Xing
Aiying Xing
Zihui Li
Zihui Li
Zihui Li
Lanyue Zhang
Lanyue Zhang
Lanyue Zhang
Liping Pan
Liping Pan
Liping Pan
Zongde Zhang
Zongde Zhang
Zongde Zhang
author_facet Jing Dong
Jing Dong
Jing Dong
Ruixue Song
Ruixue Song
Ruixue Song
Xuetian Shang
Xuetian Shang
Xuetian Shang
Yingchao Wang
Yingchao Wang
Yingchao Wang
Qiuyue Liu
Qiuyue Liu
Zhiguo Zhang
Hongyan Jia
Hongyan Jia
Hongyan Jia
Mailing Huang
Mailing Huang
Chuanzhi Zhu
Chuanzhi Zhu
Chuanzhi Zhu
Qi Sun
Qi Sun
Qi Sun
Boping Du
Boping Du
Boping Du
Aiying Xing
Aiying Xing
Aiying Xing
Zihui Li
Zihui Li
Zihui Li
Lanyue Zhang
Lanyue Zhang
Lanyue Zhang
Liping Pan
Liping Pan
Liping Pan
Zongde Zhang
Zongde Zhang
Zongde Zhang
author_sort Jing Dong
collection DOAJ
description BackgroundTuberculosis (TB) is a significant public health concern, particularly in China. Long noncoding RNAs (lncRNAs) can provide abundant pathological information regarding etiology and could include candidate biomarkers for diagnosis of TB. However, data regarding lncRNA expression profiles and specific lncRNAs associated with TB are limited.MethodsWe performed ceRNA-microarray analysis to determine the expression profile of lncRNAs in peripheral blood mononuclear cells (PBMCs). Weighted gene co-expression network analysis (WGCNA) was then conducted to identify the critical module and genes associated with TB. Other bioinformatics analyses, including Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and co-expression networks, were conducted to explore the function of the critical module. Finally, real-time quantitative polymerase chain reaction (qPCR) was used to validate the candidate biomarkers, and receiver operating characteristic analysis was used to assess the diagnostic performance of the candidate biomarkers.ResultsBased on 8 TB patients and 9 healthy controls (HCs), a total of 1,372 differentially expressed lncRNAs were identified, including 738 upregulated lncRNAs and 634 downregulated lncRNAs. Among all lncRNAs and mRNAs in the microarray, the top 25% lncRNAs (3729) and top 25% mRNAs (2824), which exhibited higher median expression values, were incorporated into the WGCNA. The analysis generated 16 co-expression modules, among which the blue module was highly correlated with TB. GO and KEGG analyses showed that the blue module was significantly enriched in infection and immunity. Subsequently, considering module membership values (>0.85), gene significance values (>0.90) and fold-change value (>2 or < 0.5) as selection criteria, the top 10 upregulated lncRNAs and top 10 downregulated lncRNAs in the blue module were considered as potential biomarkers. The candidates were then validated in an independent validation sample set (31 TB patients and 32 HCs). The expression levels of 8 candidates differed significantly between TB patients and HCs. The lncRNAs ABHD17B (area under the curve [AUC] = 1.000) and ENST00000607464.1 (AUC = 1.000) were the best lncRNAs in distinguishing TB patients from HCs.ConclusionThis study characterized the lncRNA profiles of TB patients and identified a significant module associated with TB as well as novel potential biomarkers for TB diagnosis.
first_indexed 2024-03-08T04:45:48Z
format Article
id doaj.art-701b1824b77b41d68d5127ade07b8adf
institution Directory Open Access Journal
issn 1664-302X
language English
last_indexed 2024-03-08T04:45:48Z
publishDate 2024-02-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Microbiology
spelling doaj.art-701b1824b77b41d68d5127ade07b8adf2024-02-08T09:24:50ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2024-02-011510.3389/fmicb.2024.13541901354190Identification of important modules and biomarkers in tuberculosis based on WGCNAJing Dong0Jing Dong1Jing Dong2Ruixue Song3Ruixue Song4Ruixue Song5Xuetian Shang6Xuetian Shang7Xuetian Shang8Yingchao Wang9Yingchao Wang10Yingchao Wang11Qiuyue Liu12Qiuyue Liu13Zhiguo Zhang14Hongyan Jia15Hongyan Jia16Hongyan Jia17Mailing Huang18Mailing Huang19Chuanzhi Zhu20Chuanzhi Zhu21Chuanzhi Zhu22Qi Sun23Qi Sun24Qi Sun25Boping Du26Boping Du27Boping Du28Aiying Xing29Aiying Xing30Aiying Xing31Zihui Li32Zihui Li33Zihui Li34Lanyue Zhang35Lanyue Zhang36Lanyue Zhang37Liping Pan38Liping Pan39Liping Pan40Zongde Zhang41Zongde Zhang42Zongde Zhang43Beijing Chest Hospital, Capital Medical University, Beijing, ChinaBeijing Key Laboratory for Drug Resistant Tuberculosis Research, Beijing, ChinaBeijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, ChinaBeijing Chest Hospital, Capital Medical University, Beijing, ChinaBeijing Key Laboratory for Drug Resistant Tuberculosis Research, Beijing, ChinaBeijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, ChinaBeijing Chest Hospital, Capital Medical University, Beijing, ChinaBeijing Key Laboratory for Drug Resistant Tuberculosis Research, Beijing, ChinaBeijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, ChinaBeijing Chest Hospital, Capital Medical University, Beijing, ChinaBeijing Key Laboratory for Drug Resistant Tuberculosis Research, Beijing, ChinaBeijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, ChinaBeijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, ChinaDepartment of Intensive Care Unit, Beijing Chest Hospital, Capital Medical University, Beijing, ChinaChangping Tuberculosis Prevent and Control Institute of Beijing, Beijing, ChinaBeijing Chest Hospital, Capital Medical University, Beijing, ChinaBeijing Key Laboratory for Drug Resistant Tuberculosis Research, Beijing, ChinaBeijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, ChinaBeijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, ChinaDepartment of Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing, ChinaBeijing Chest Hospital, Capital Medical University, Beijing, ChinaBeijing Key Laboratory for Drug Resistant Tuberculosis Research, Beijing, ChinaBeijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, ChinaBeijing Chest Hospital, Capital Medical University, Beijing, ChinaBeijing Key Laboratory for Drug Resistant Tuberculosis Research, Beijing, ChinaBeijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, ChinaBeijing Chest Hospital, Capital Medical University, Beijing, ChinaBeijing Key Laboratory for Drug Resistant Tuberculosis Research, Beijing, ChinaBeijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, ChinaBeijing Chest Hospital, Capital Medical University, Beijing, ChinaBeijing Key Laboratory for Drug Resistant Tuberculosis Research, Beijing, ChinaBeijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, ChinaBeijing Chest Hospital, Capital Medical University, Beijing, ChinaBeijing Key Laboratory for Drug Resistant Tuberculosis Research, Beijing, ChinaBeijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, ChinaBeijing Chest Hospital, Capital Medical University, Beijing, ChinaBeijing Key Laboratory for Drug Resistant Tuberculosis Research, Beijing, ChinaBeijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, ChinaBeijing Chest Hospital, Capital Medical University, Beijing, ChinaBeijing Key Laboratory for Drug Resistant Tuberculosis Research, Beijing, ChinaBeijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, ChinaBeijing Chest Hospital, Capital Medical University, Beijing, ChinaBeijing Key Laboratory for Drug Resistant Tuberculosis Research, Beijing, ChinaBeijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, ChinaBackgroundTuberculosis (TB) is a significant public health concern, particularly in China. Long noncoding RNAs (lncRNAs) can provide abundant pathological information regarding etiology and could include candidate biomarkers for diagnosis of TB. However, data regarding lncRNA expression profiles and specific lncRNAs associated with TB are limited.MethodsWe performed ceRNA-microarray analysis to determine the expression profile of lncRNAs in peripheral blood mononuclear cells (PBMCs). Weighted gene co-expression network analysis (WGCNA) was then conducted to identify the critical module and genes associated with TB. Other bioinformatics analyses, including Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and co-expression networks, were conducted to explore the function of the critical module. Finally, real-time quantitative polymerase chain reaction (qPCR) was used to validate the candidate biomarkers, and receiver operating characteristic analysis was used to assess the diagnostic performance of the candidate biomarkers.ResultsBased on 8 TB patients and 9 healthy controls (HCs), a total of 1,372 differentially expressed lncRNAs were identified, including 738 upregulated lncRNAs and 634 downregulated lncRNAs. Among all lncRNAs and mRNAs in the microarray, the top 25% lncRNAs (3729) and top 25% mRNAs (2824), which exhibited higher median expression values, were incorporated into the WGCNA. The analysis generated 16 co-expression modules, among which the blue module was highly correlated with TB. GO and KEGG analyses showed that the blue module was significantly enriched in infection and immunity. Subsequently, considering module membership values (>0.85), gene significance values (>0.90) and fold-change value (>2 or < 0.5) as selection criteria, the top 10 upregulated lncRNAs and top 10 downregulated lncRNAs in the blue module were considered as potential biomarkers. The candidates were then validated in an independent validation sample set (31 TB patients and 32 HCs). The expression levels of 8 candidates differed significantly between TB patients and HCs. The lncRNAs ABHD17B (area under the curve [AUC] = 1.000) and ENST00000607464.1 (AUC = 1.000) were the best lncRNAs in distinguishing TB patients from HCs.ConclusionThis study characterized the lncRNA profiles of TB patients and identified a significant module associated with TB as well as novel potential biomarkers for TB diagnosis.https://www.frontiersin.org/articles/10.3389/fmicb.2024.1354190/fulltuberculosislncRNAmRNAWGCNAdiagnosis
spellingShingle Jing Dong
Jing Dong
Jing Dong
Ruixue Song
Ruixue Song
Ruixue Song
Xuetian Shang
Xuetian Shang
Xuetian Shang
Yingchao Wang
Yingchao Wang
Yingchao Wang
Qiuyue Liu
Qiuyue Liu
Zhiguo Zhang
Hongyan Jia
Hongyan Jia
Hongyan Jia
Mailing Huang
Mailing Huang
Chuanzhi Zhu
Chuanzhi Zhu
Chuanzhi Zhu
Qi Sun
Qi Sun
Qi Sun
Boping Du
Boping Du
Boping Du
Aiying Xing
Aiying Xing
Aiying Xing
Zihui Li
Zihui Li
Zihui Li
Lanyue Zhang
Lanyue Zhang
Lanyue Zhang
Liping Pan
Liping Pan
Liping Pan
Zongde Zhang
Zongde Zhang
Zongde Zhang
Identification of important modules and biomarkers in tuberculosis based on WGCNA
Frontiers in Microbiology
tuberculosis
lncRNA
mRNA
WGCNA
diagnosis
title Identification of important modules and biomarkers in tuberculosis based on WGCNA
title_full Identification of important modules and biomarkers in tuberculosis based on WGCNA
title_fullStr Identification of important modules and biomarkers in tuberculosis based on WGCNA
title_full_unstemmed Identification of important modules and biomarkers in tuberculosis based on WGCNA
title_short Identification of important modules and biomarkers in tuberculosis based on WGCNA
title_sort identification of important modules and biomarkers in tuberculosis based on wgcna
topic tuberculosis
lncRNA
mRNA
WGCNA
diagnosis
url https://www.frontiersin.org/articles/10.3389/fmicb.2024.1354190/full
work_keys_str_mv AT jingdong identificationofimportantmodulesandbiomarkersintuberculosisbasedonwgcna
AT jingdong identificationofimportantmodulesandbiomarkersintuberculosisbasedonwgcna
AT jingdong identificationofimportantmodulesandbiomarkersintuberculosisbasedonwgcna
AT ruixuesong identificationofimportantmodulesandbiomarkersintuberculosisbasedonwgcna
AT ruixuesong identificationofimportantmodulesandbiomarkersintuberculosisbasedonwgcna
AT ruixuesong identificationofimportantmodulesandbiomarkersintuberculosisbasedonwgcna
AT xuetianshang identificationofimportantmodulesandbiomarkersintuberculosisbasedonwgcna
AT xuetianshang identificationofimportantmodulesandbiomarkersintuberculosisbasedonwgcna
AT xuetianshang identificationofimportantmodulesandbiomarkersintuberculosisbasedonwgcna
AT yingchaowang identificationofimportantmodulesandbiomarkersintuberculosisbasedonwgcna
AT yingchaowang identificationofimportantmodulesandbiomarkersintuberculosisbasedonwgcna
AT yingchaowang identificationofimportantmodulesandbiomarkersintuberculosisbasedonwgcna
AT qiuyueliu identificationofimportantmodulesandbiomarkersintuberculosisbasedonwgcna
AT qiuyueliu identificationofimportantmodulesandbiomarkersintuberculosisbasedonwgcna
AT zhiguozhang identificationofimportantmodulesandbiomarkersintuberculosisbasedonwgcna
AT hongyanjia identificationofimportantmodulesandbiomarkersintuberculosisbasedonwgcna
AT hongyanjia identificationofimportantmodulesandbiomarkersintuberculosisbasedonwgcna
AT hongyanjia identificationofimportantmodulesandbiomarkersintuberculosisbasedonwgcna
AT mailinghuang identificationofimportantmodulesandbiomarkersintuberculosisbasedonwgcna
AT mailinghuang identificationofimportantmodulesandbiomarkersintuberculosisbasedonwgcna
AT chuanzhizhu identificationofimportantmodulesandbiomarkersintuberculosisbasedonwgcna
AT chuanzhizhu identificationofimportantmodulesandbiomarkersintuberculosisbasedonwgcna
AT chuanzhizhu identificationofimportantmodulesandbiomarkersintuberculosisbasedonwgcna
AT qisun identificationofimportantmodulesandbiomarkersintuberculosisbasedonwgcna
AT qisun identificationofimportantmodulesandbiomarkersintuberculosisbasedonwgcna
AT qisun identificationofimportantmodulesandbiomarkersintuberculosisbasedonwgcna
AT bopingdu identificationofimportantmodulesandbiomarkersintuberculosisbasedonwgcna
AT bopingdu identificationofimportantmodulesandbiomarkersintuberculosisbasedonwgcna
AT bopingdu identificationofimportantmodulesandbiomarkersintuberculosisbasedonwgcna
AT aiyingxing identificationofimportantmodulesandbiomarkersintuberculosisbasedonwgcna
AT aiyingxing identificationofimportantmodulesandbiomarkersintuberculosisbasedonwgcna
AT aiyingxing identificationofimportantmodulesandbiomarkersintuberculosisbasedonwgcna
AT zihuili identificationofimportantmodulesandbiomarkersintuberculosisbasedonwgcna
AT zihuili identificationofimportantmodulesandbiomarkersintuberculosisbasedonwgcna
AT zihuili identificationofimportantmodulesandbiomarkersintuberculosisbasedonwgcna
AT lanyuezhang identificationofimportantmodulesandbiomarkersintuberculosisbasedonwgcna
AT lanyuezhang identificationofimportantmodulesandbiomarkersintuberculosisbasedonwgcna
AT lanyuezhang identificationofimportantmodulesandbiomarkersintuberculosisbasedonwgcna
AT lipingpan identificationofimportantmodulesandbiomarkersintuberculosisbasedonwgcna
AT lipingpan identificationofimportantmodulesandbiomarkersintuberculosisbasedonwgcna
AT lipingpan identificationofimportantmodulesandbiomarkersintuberculosisbasedonwgcna
AT zongdezhang identificationofimportantmodulesandbiomarkersintuberculosisbasedonwgcna
AT zongdezhang identificationofimportantmodulesandbiomarkersintuberculosisbasedonwgcna
AT zongdezhang identificationofimportantmodulesandbiomarkersintuberculosisbasedonwgcna