Exploring TSPAN4 promoter methylation as a diagnostic biomarker for tuberculosis

Zhang, Jiahao1,2,3,4; Chen, Jilong1,2,3,4; Zhang, Yan1,2,3,4; Chen, Liuchi1,2,3,4; Mo, Weiwei1,2,3,4; Yang, Qianting5,6; Zhang, Mingxia5,6; Liu, Haiying1,2,3,4

2024-04-12

10.3389/fgene.2024.1380828

FRONTIERS IN GENETICS   影响因子和分区

1664-8021

Background: Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a persistent infectious disease threatening human health. The existing diagnostic methods still have significant shortcomings, including a low positivity rate in pathogen-based diagnoses and the inability of immunological diagnostics to detect active TB. Hence, it is urgent to develop new techniques to detect TB more accurate and earlier. This research aims to scrutinize and authenticate DNA methylation markers suitable for tuberculosis diagnosis. Concurrently, Providing a new approach for tuberculosis diagnosis.Methods: Blood samples from patients with newly diagnosed tuberculosis and healthy controls (HC) were utilized in this study. Examining methylation microarray data from 40 whole blood samples (22TB + 18HC), we employed two procedures: signature gene methylated position analysis and signature region methylated position analysis to pinpoint distinctive methylated positions. Based on the screening results, diagnostic classifiers are constructed through machine learning, and validation was conducted through pyrosequencing in a separate queue (22TB + 18HC). Culminating in the development of a new tuberculosis diagnostic method via quantitative real-time methylation specific PCR (qMSP).Results: The combination of the two procedures revealed a total of 10 methylated positions, all of which were located in the promoter region. These 10 signature methylated positions facilitated the construction of a diagnostic classifier, exhibiting robust diagnostic accuracy in both cross-validation and external test sets. The LDA model demonstrated the best classification performance, achieving an AUC of 0.83, specificity of 0.8, and sensitivity of 0.86 on the external test set. Furthermore, the validation of signature methylated positions through pyrosequencing demonstrated high agreement with screening outcomes. Additionally, qMSP detection of 2 potential hypomethylated positions (cg04552852 and cg12464638) exhibited promising results, yielding an AUC of 0.794, specificity of 0.720, and sensitivity of 0.816.Conclusion: Our study demonstrates that the validated signature methylated positions through pyrosequencing emerge as plausible biomarkers for tuberculosis diagnosis. The specific methylation markers in the TSPAN4 gene, identified in whole blood samples, hold promise for improving tuberculosis diagnosis. This approach could significantly enhance diagnostic accuracy and speed, offering a new avenue for early detection and treatment.

tuberculosis DNA methylation biomarkers diagnosis machine learning qMSP

SCI

英语

其他

National Key R&D Program of China["2021YFA1300904","82070015"] ; CAMS Innovation Fund for Medical Sciences (CIFMS)[2021-I2M-1-037]

Genetics & Heredity

Genetics & Heredity

WOS:001208460400001

FRONTIERS MEDIA SA

Web of Science

1.Chinese Acad Med Sci & Peking Union Med Coll, Natl Inst Pathogen Biol, Beijing, Peoples R China
2.Chinese Acad Med Sci & Peking Union Med Coll, Natl Inst Pathogen Biol, State Key Lab Resp Hlth & Multimorbid, NHC Key Lab Syst Biol Pathogens, Beijing, Peoples R China
3.Chinese Acad Med Sci & Peking Union Med Coll, Natl Inst Pathogen Biol, Beijing, Peoples R China
4.Chinese Acad Med Sci & Peking Union Med Coll, Ctr TB Res, Beijing, Peoples R China
5.Shenzhen Clin Res Ctr TB, Shenzhen, Peoples R China
6.Southern Univ Sci & Technol, Shenzhen Peoples Hosp 3, Affiliated Hosp 2, Inst Hepatol,Natl Clin Res Ctr Infect Dis, Shenzhen, Peoples R China

Zhang, Jiahao,Chen, Jilong,Zhang, Yan,et al. Exploring TSPAN4 promoter methylation as a diagnostic biomarker for tuberculosis[J]. FRONTIERS IN GENETICS,2024,15.

Zhang, Jiahao.,Chen, Jilong.,Zhang, Yan.,Chen, Liuchi.,Mo, Weiwei.,...&Liu, Haiying.(2024).Exploring TSPAN4 promoter methylation as a diagnostic biomarker for tuberculosis.FRONTIERS IN GENETICS,15.

Zhang, Jiahao,et al."Exploring TSPAN4 promoter methylation as a diagnostic biomarker for tuberculosis".FRONTIERS IN GENETICS 15(2024).