Epigenetics and Proteomics Join Transcriptomics in the Quest for Tuberculosis Biomarkers

ABSTRACT An estimated one-third of the world's population is currently latently infected with Mycobacterium tuberculosis. Latent M. tuberculosis infection (LTBI) progresses into active tuberculosis (TB) disease in ~5 to 10% of infected individuals. Diagnostic and prognostic biomarkers to monito...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Maria M. Esterhuyse, January Weiner, Etienne Caron, Andre G. Loxton, Marco Iannaccone, Chandre Wagman, Philippe Saikali, Kim Stanley, Witold E. Wolski, Hans-Joachim Mollenkopf, Matthias Schick, Ruedi Aebersold, Heinz Linhart, Gerhard Walzl, Stefan H. E. Kaufmann
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2015
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/a7f947a744f5488f8d08a4f99989053d
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:a7f947a744f5488f8d08a4f99989053d
record_format	dspace
spelling	oai:doaj.org-article:a7f947a744f5488f8d08a4f99989053d2021-11-15T15:41:30ZEpigenetics and Proteomics Join Transcriptomics in the Quest for Tuberculosis Biomarkers10.1128/mBio.01187-152150-7511https://doaj.org/article/a7f947a744f5488f8d08a4f99989053d2015-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01187-15https://doaj.org/toc/2150-7511ABSTRACT An estimated one-third of the world's population is currently latently infected with Mycobacterium tuberculosis. Latent M. tuberculosis infection (LTBI) progresses into active tuberculosis (TB) disease in ~5 to 10% of infected individuals. Diagnostic and prognostic biomarkers to monitor disease progression are urgently needed to ensure better care for TB patients and to decrease the spread of TB. Biomarker development is primarily based on transcriptomics. Our understanding of biology combined with evolving technical advances in high-throughput techniques led us to investigate the possibility of additional platforms (epigenetics and proteomics) in the quest to (i) understand the biology of the TB host response and (ii) search for multiplatform biosignatures in TB. We engaged in a pilot study to interrogate the DNA methylome, transcriptome, and proteome in selected monocytes and granulocytes from TB patients and healthy LTBI participants. Our study provides first insights into the levels and sources of diversity in the epigenome and proteome among TB patients and LTBI controls, despite limitations due to small sample size. Functionally the differences between the infection phenotypes (LTBI versus active TB) observed in the different platforms were congruent, thereby suggesting regulation of function not only at the transcriptional level but also by DNA methylation and microRNA. Thus, our data argue for the development of a large-scale study of the DNA methylome, with particular attention to study design in accounting for variation based on gender, age, and cell type. IMPORTANCE DNA methylation modifies the transcriptional program of cells. We have focused on two major populations of leukocytes involved in immune response to infectious diseases, granulocytes and monocytes, both of which are professional phagocytes that engulf and kill bacteria. We have interrogated how DNA methylation, gene expression, and protein translation differ in these two cell populations between healthy individuals and patients suffering from TB. To better understand the underlying biologic mechanisms, we harnessed a statistical enrichment analysis, taking advantage of predefined and well-characterized gene sets. Not only were there clear differences on various levels between the two populations, but there were also differences between TB patients and healthy controls in the transcriptome, proteome, and, for the first time, DNA methylome in these cells. Our pilot study emphasizes the value of a large-scale study of the DNA methylome taking into account our findings.Maria M. EsterhuyseJanuary WeinerEtienne CaronAndre G. LoxtonMarco IannacconeChandre WagmanPhilippe SaikaliKim StanleyWitold E. WolskiHans-Joachim MollenkopfMatthias SchickRuedi AebersoldHeinz LinhartGerhard WalzlStefan H. E. KaufmannAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 6, Iss 5 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Maria M. Esterhuyse January Weiner Etienne Caron Andre G. Loxton Marco Iannaccone Chandre Wagman Philippe Saikali Kim Stanley Witold E. Wolski Hans-Joachim Mollenkopf Matthias Schick Ruedi Aebersold Heinz Linhart Gerhard Walzl Stefan H. E. Kaufmann Epigenetics and Proteomics Join Transcriptomics in the Quest for Tuberculosis Biomarkers
description	ABSTRACT An estimated one-third of the world's population is currently latently infected with Mycobacterium tuberculosis. Latent M. tuberculosis infection (LTBI) progresses into active tuberculosis (TB) disease in ~5 to 10% of infected individuals. Diagnostic and prognostic biomarkers to monitor disease progression are urgently needed to ensure better care for TB patients and to decrease the spread of TB. Biomarker development is primarily based on transcriptomics. Our understanding of biology combined with evolving technical advances in high-throughput techniques led us to investigate the possibility of additional platforms (epigenetics and proteomics) in the quest to (i) understand the biology of the TB host response and (ii) search for multiplatform biosignatures in TB. We engaged in a pilot study to interrogate the DNA methylome, transcriptome, and proteome in selected monocytes and granulocytes from TB patients and healthy LTBI participants. Our study provides first insights into the levels and sources of diversity in the epigenome and proteome among TB patients and LTBI controls, despite limitations due to small sample size. Functionally the differences between the infection phenotypes (LTBI versus active TB) observed in the different platforms were congruent, thereby suggesting regulation of function not only at the transcriptional level but also by DNA methylation and microRNA. Thus, our data argue for the development of a large-scale study of the DNA methylome, with particular attention to study design in accounting for variation based on gender, age, and cell type. IMPORTANCE DNA methylation modifies the transcriptional program of cells. We have focused on two major populations of leukocytes involved in immune response to infectious diseases, granulocytes and monocytes, both of which are professional phagocytes that engulf and kill bacteria. We have interrogated how DNA methylation, gene expression, and protein translation differ in these two cell populations between healthy individuals and patients suffering from TB. To better understand the underlying biologic mechanisms, we harnessed a statistical enrichment analysis, taking advantage of predefined and well-characterized gene sets. Not only were there clear differences on various levels between the two populations, but there were also differences between TB patients and healthy controls in the transcriptome, proteome, and, for the first time, DNA methylome in these cells. Our pilot study emphasizes the value of a large-scale study of the DNA methylome taking into account our findings.
format	article
author	Maria M. Esterhuyse January Weiner Etienne Caron Andre G. Loxton Marco Iannaccone Chandre Wagman Philippe Saikali Kim Stanley Witold E. Wolski Hans-Joachim Mollenkopf Matthias Schick Ruedi Aebersold Heinz Linhart Gerhard Walzl Stefan H. E. Kaufmann
author_facet	Maria M. Esterhuyse January Weiner Etienne Caron Andre G. Loxton Marco Iannaccone Chandre Wagman Philippe Saikali Kim Stanley Witold E. Wolski Hans-Joachim Mollenkopf Matthias Schick Ruedi Aebersold Heinz Linhart Gerhard Walzl Stefan H. E. Kaufmann
author_sort	Maria M. Esterhuyse
title	Epigenetics and Proteomics Join Transcriptomics in the Quest for Tuberculosis Biomarkers
title_short	Epigenetics and Proteomics Join Transcriptomics in the Quest for Tuberculosis Biomarkers
title_full	Epigenetics and Proteomics Join Transcriptomics in the Quest for Tuberculosis Biomarkers
title_fullStr	Epigenetics and Proteomics Join Transcriptomics in the Quest for Tuberculosis Biomarkers
title_full_unstemmed	Epigenetics and Proteomics Join Transcriptomics in the Quest for Tuberculosis Biomarkers
title_sort	epigenetics and proteomics join transcriptomics in the quest for tuberculosis biomarkers
publisher	American Society for Microbiology
publishDate	2015
url	https://doaj.org/article/a7f947a744f5488f8d08a4f99989053d
work_keys_str_mv	AT mariamesterhuyse epigeneticsandproteomicsjointranscriptomicsinthequestfortuberculosisbiomarkers AT januaryweiner epigeneticsandproteomicsjointranscriptomicsinthequestfortuberculosisbiomarkers AT etiennecaron epigeneticsandproteomicsjointranscriptomicsinthequestfortuberculosisbiomarkers AT andregloxton epigeneticsandproteomicsjointranscriptomicsinthequestfortuberculosisbiomarkers AT marcoiannaccone epigeneticsandproteomicsjointranscriptomicsinthequestfortuberculosisbiomarkers AT chandrewagman epigeneticsandproteomicsjointranscriptomicsinthequestfortuberculosisbiomarkers AT philippesaikali epigeneticsandproteomicsjointranscriptomicsinthequestfortuberculosisbiomarkers AT kimstanley epigeneticsandproteomicsjointranscriptomicsinthequestfortuberculosisbiomarkers AT witoldewolski epigeneticsandproteomicsjointranscriptomicsinthequestfortuberculosisbiomarkers AT hansjoachimmollenkopf epigeneticsandproteomicsjointranscriptomicsinthequestfortuberculosisbiomarkers AT matthiasschick epigeneticsandproteomicsjointranscriptomicsinthequestfortuberculosisbiomarkers AT ruediaebersold epigeneticsandproteomicsjointranscriptomicsinthequestfortuberculosisbiomarkers AT heinzlinhart epigeneticsandproteomicsjointranscriptomicsinthequestfortuberculosisbiomarkers AT gerhardwalzl epigeneticsandproteomicsjointranscriptomicsinthequestfortuberculosisbiomarkers AT stefanhekaufmann epigeneticsandproteomicsjointranscriptomicsinthequestfortuberculosisbiomarkers
_version_	1718427720906440704

Epigenetics and Proteomics Join Transcriptomics in the Quest for Tuberculosis Biomarkers

Ejemplares similares