Integrative multi-omics reveals serum markers of tuberculosis in advanced HIV

National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award numbers UM1 AI068634, UM1 AI068636, and UM1 AI106701

Bibliographic Details
Authors: Krishnan, Sonya, Queiroz, Artur Trancoso Lopo de, Gupta, Amita, Gupte, Nikhil, Bisson, Gregory P., Kumwenda, Johnstone, Naidoo, Kogieleum, Mohapi, Lerato, Mave, Vidya, Mngqibisa, Rosie, Lama, Javier R., Hosseinipour, Mina C., Andrade, Bruno de Bezerril, Karakousis, Petros C.
Format: article
Status:Published version
Publication Date:2021
Country:Brasil
Institution:Fundação Oswaldo Cruz (FIOCRUZ)
Repository:Repositório Institucional da FIOCRUZ (ARCA)
Language:English
OAI Identifier:oai:arca.fiocruz.br:icict/48078
Online Access:https://arca.fiocruz.br/handle/icict/48078
Access Level:Open access
Keyword:Tuberculose
HIV
MicroRNAs
Metabolômica
Biomarcadores
Tuberculosis
MicroRNA
Metabolomics
Biomarker
Multi-omics
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dc.title.none.fl_str_mv Integrative multi-omics reveals serum markers of tuberculosis in advanced HIV
title Integrative multi-omics reveals serum markers of tuberculosis in advanced HIV
spellingShingle Integrative multi-omics reveals serum markers of tuberculosis in advanced HIV
Krishnan, Sonya
Tuberculose
HIV
MicroRNAs
Metabolômica
Biomarcadores
Tuberculosis
HIV
MicroRNA
Metabolomics
Biomarker
Multi-omics
title_short Integrative multi-omics reveals serum markers of tuberculosis in advanced HIV
title_full Integrative multi-omics reveals serum markers of tuberculosis in advanced HIV
title_fullStr Integrative multi-omics reveals serum markers of tuberculosis in advanced HIV
title_full_unstemmed Integrative multi-omics reveals serum markers of tuberculosis in advanced HIV
title_sort Integrative multi-omics reveals serum markers of tuberculosis in advanced HIV
dc.creator.none.fl_str_mv Krishnan, Sonya
Queiroz, Artur Trancoso Lopo de
Gupta, Amita
Gupte, Nikhil
Bisson, Gregory P.
Kumwenda, Johnstone
Naidoo, Kogieleum
Mohapi, Lerato
Mave, Vidya
Mngqibisa, Rosie
Lama, Javier R.
Hosseinipour, Mina C.
Andrade, Bruno de Bezerril
Karakousis, Petros C.
author Krishnan, Sonya
author_facet Krishnan, Sonya
Queiroz, Artur Trancoso Lopo de
Gupta, Amita
Gupte, Nikhil
Bisson, Gregory P.
Kumwenda, Johnstone
Naidoo, Kogieleum
Mohapi, Lerato
Mave, Vidya
Mngqibisa, Rosie
Lama, Javier R.
Hosseinipour, Mina C.
Andrade, Bruno de Bezerril
Karakousis, Petros C.
author_role author
author2 Queiroz, Artur Trancoso Lopo de
Gupta, Amita
Gupte, Nikhil
Bisson, Gregory P.
Kumwenda, Johnstone
Naidoo, Kogieleum
Mohapi, Lerato
Mave, Vidya
Mngqibisa, Rosie
Lama, Javier R.
Hosseinipour, Mina C.
Andrade, Bruno de Bezerril
Karakousis, Petros C.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.other.none.fl_str_mv Tuberculose
HIV
MicroRNAs
Metabolômica
Biomarcadores
topic Tuberculose
HIV
MicroRNAs
Metabolômica
Biomarcadores
Tuberculosis
HIV
MicroRNA
Metabolomics
Biomarker
Multi-omics
dc.subject.en.none.fl_str_mv Tuberculosis
HIV
MicroRNA
Metabolomics
Biomarker
Multi-omics
description National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award numbers UM1 AI068634, UM1 AI068636, and UM1 AI106701
publishDate 2021
dc.date.accessioned.fl_str_mv 2021-07-08T18:52:20Z
dc.date.available.fl_str_mv 2021-07-08T18:52:20Z
dc.date.issued.fl_str_mv 2021
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv KRISHNAN, Sonya et al. Integrative multi-omics reveals serum markers of tuberculosis in advanced HIV. Frontiers in Immunology, p. 1-10, 8 June 2021.
dc.identifier.uri.fl_str_mv https://arca.fiocruz.br/handle/icict/48078
dc.identifier.issn.none.fl_str_mv 1664-3224
dc.identifier.doi.none.fl_str_mv 10.3389/fimmu.2021.676980
identifier_str_mv KRISHNAN, Sonya et al. Integrative multi-omics reveals serum markers of tuberculosis in advanced HIV. Frontiers in Immunology, p. 1-10, 8 June 2021.
1664-3224
10.3389/fimmu.2021.676980
url https://arca.fiocruz.br/handle/icict/48078
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
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spelling 2021-07-08T18:52:20Z2021-07-08T18:52:20Z2021KRISHNAN, Sonya et al. Integrative multi-omics reveals serum markers of tuberculosis in advanced HIV. Frontiers in Immunology, p. 1-10, 8 June 2021.1664-3224https://arca.fiocruz.br/handle/icict/4807810.3389/fimmu.2021.676980National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award numbers UM1 AI068634, UM1 AI068636, and UM1 AI106701Johns Hopkins Baltimore-Washington-India Clinical Trials Unit (BWI CTU) (NIH/NIAID UM1AI069465)AIDS Clinical Trials Group (ACTG) and CRDF GlobalJohns Hopkins University Center for AIDS Research (P30AI094189)National Institute of Health T32 AI007291-27NIH/NIAID grant K24AI143447Johns Hopkins University School of Medicine. Center for Clinical Global Health Education and Center for Tuberculosis Research. Department of Medicine. Division of Infectious Diseases. Baltimore, MD, United States.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research. Salvador, BA, Brasil.Johns Hopkins University School of Medicine. Center for Clinical Global Health Education and Center for Tuberculosis Research. Department of Medicine. Division of Infectious Diseases. Baltimore, MD, United States / Johns Hopkins University Clinical Research Site. Byramjee Jeejeebhoy Government Medical College. Pune, India / Johns Hopkins Bloomberg School of Public Health. Department of International Health. Baltimore, MD, United States.Johns Hopkins University School of Medicine. Center for Clinical Global Health Education and Center for Tuberculosis Research. Department of Medicine. Division of Infectious Diseases. Baltimore, MD, United States / Johns Hopkins University Clinical Research Site. Byramjee Jeejeebhoy Government Medical College. Pune, India.University of Pennsylvania. Perelman School of Medicine. Department of Medicine. Division of Infectious Diseases. Philadelphia, PA, United States.College of Medicine-Johns Hopkins Project. Blantyre, Malawi.University of KwaZulu-Natal. Centre for the AIDS Programme of Research in South Africa. Nelson R. Mandela School of Medicine. College of Health Sciences. Durban, South Africa / University of KwaZulu-Natal. Doris Duke Medical Research Institute. South African Medical Research Council Pathogenesis and Treatment Research Unit. Durban, South Africa.University of the Witwatersrand. Perinatal HIV Research Unit. Johannesburg, South Africa.Johns Hopkins University Clinical Research Site. Byramjee Jeejeebhoy Government Medical College. Pune, India.Enhancing Care Foundation. Durban International Clinical Research Site. Durban, South Africa.Asociacion Civil Impacta Salud y Educacion. Lima, Peru.University of North Carolina. Project-Malawi. Lilongwe, Malawi / University of North Carolina. Department of Medicine. Division of Infectious Diseases. Chapel Hill, NC, United States.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil / Faculdade de Tecnologia e Ciências. Curso de Medicina. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Curso de Medicina. Salvador, BA, Brasil.Johns Hopkins University School of Medicine. Center for Clinical Global Health Education and Center for Tuberculosis Research. Department of Medicine. Division of Infectious Diseases. Baltimore, MD, United States / Johns Hopkins Bloomberg School of Public Health. Department of International Health. Baltimore, MD, United States.Tuberculosis (TB) accounts for disproportionate morbidity and mortality among persons living with HIV (PLWH). Conventional methods of TB diagnosis, including smear microscopy and Xpert MTB/RIF, have lower sensitivity in PLWH. Novel high-throughput approaches, such as miRNAomics and metabolomics, may advance our ability to recognize subclinical and difficult-to-diagnose TB, especially in very advanced HIV. We conducted a case-control study leveraging REMEMBER, a multi-country, open-label randomized controlled trial comparing 4-drug empiric standard TB treatment with isoniazid preventive therapy in PLWH initiating antiretroviral therapy (ART) with CD4 cell counts <50 cells/mL. Twenty-three cases of incident TB were site-matched with 32 controls to identify microRNAs (miRNAs), metabolites, and cytokines/chemokines, associated with the development of newly diagnosed TB in PLWH. Differentially expressed miRNA analysis revealed 11 altered miRNAs with a fold change higher than 1.4 or lower than -1.4 in cases relative to controls (p<0.05). Our analysis revealed no differentially abundant metabolites between cases and controls. We found higher TNFa and IP-10/CXCL10 in cases (p=0.011, p=0.0005), and higher MDC/CCL22 in controls (p=0.0072). A decision-tree algorithm identified gamma-glutamylthreonine and hsa-miR215-5p as the optimal variables to classify incident TB cases (AUC 0.965; 95% CI 0.925-1.000). hsa-miR-215-5p, which targets genes in the TGF-b signaling pathway, was downregulated in cases. Gamma-glutamylthreonine, a breakdown product of protein catabolism, was less abundant in cases. 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