Author | Kulkarni, Vandana | |
Author | Queiroz, Artur Trancoso Lopo de | |
Author | Sangle, Shashi | |
Author | Kagal, Anju | |
Author | Salvi, Sonali | |
Author | Gupta, Amita | |
Author | Ellner, Jerrold | |
Author | Kadam, Dileep | |
Author | Rolla, Valeria C. | |
Author | Andrade, Bruno de Bezerril | |
Author | Salgame, Padmini | |
Author | Mave, Vidya | |
Access date | 2021-04-07T11:48:44Z | |
Available date | 2021-04-07T11:48:44Z | |
Document date | 2021 | |
Citation | KULKARNI, Vandana et al. A Two-Gene Signature for Tuberculosis Diagnosis in Persons With Advanced HIV. Frontiers in Immunology, v. 12, 2021. | pt_BR |
ISSN | 1664-3224 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/46533 | |
Sponsorship | CRDF Global
(Award number DAA3-17-63158-1/Country: India). Research
data in this manuscript were collected, in part, as part of the
Regional Prospective Observational Research for Tuberculosis
(RePORT) India Consortium. This work was funded in whole
or in part by federal funds from the Government of India
Department of Biotechnology (DBT); the Indian Council of
Medical Research (ICMR); the National Institutes of Health
National Institute of Allergy and Infectious Diseases Office
of AIDS Research; CRDF Global; the National Institutes of
Health Baltimore-Washington-India Clinical Trials Unit for
National Institute of Allergy and Infectious Diseases Networks
(UM1AI069465 to VM and AG); and the National Institutes of
Health (R01A1I097494 to VM and AG). The work of BBA was
supported by the Intramural Research Program of the Oswaldo
Cruz Foundation, and the National Council for Scientific
and Technological Development (senior CNPq fellowship—tier
1D), Brazil. | pt_BR |
Language | eng | pt_BR |
Publisher | Frontiers Media | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | HIV | pt_BR |
Subject in Portuguese | Tuberculose | pt_BR |
Subject in Portuguese | Diagnóstico | pt_BR |
Subject in Portuguese | Genes | pt_BR |
Title | A Two-Gene Signature for Tuberculosis Diagnosis in Persons With Advanced HIV | pt_BR |
Type | Article | pt_BR |
DOI | 10.3389/fimmu.2021.631165 | |
Abstract | Transcriptomic signatures for tuberculosis (TB) have been proposed and
represent a promising diagnostic tool. Data remain limited in persons with advanced HIV.
Methods: We enrolled 30 patients with advanced HIV (CD4 < 100 cells/mm3) in India;
16 with active TB and 14 without. Whole-blood RNA sequencing was performed; these
data were merged with a publicly available dataset from Uganda (n = 33; 18 with TB
and 15 without). Transcriptomic profiling and machine learning algorithms identified an
optimal gene signature for TB classification. Receiver operating characteristic analysis
was used to assess performance.
Results: Among 565 differentially expressed genes identified for TB, 40 were shared
across India and Uganda cohorts. Common upregulated pathways reflect Toll-like
receptor cascades and neutrophil degranulation. The machine-learning decision-tree
algorithm selected gene expression values from RAB20 and INSL3 as most informative
for TB classification. The signature accurately classified TB in discovery cohorts
(India AUC 0.95 and Uganda AUC 1.0; p < 0.001); accuracy was fair in external
validation cohorts.
Conclusions: Expression values of RAB20 and INSL3 genes in peripheral blood
compose a biosignature that accurately classified TB status among patients with
advanced HIV in two geographically distinct cohorts. The functional analysis suggests
pathways previously reported in TB pathogenesis. | pt_BR |
Affilliation | Johns Hopkins University Clinical Research Site. Byramjee-Jeejeebhoy Government Medical College. Pune, India. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Bahia, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative, Salvador, BA, Brazil. | pt_BR |
Affilliation | Johns Hopkins University Clinical Research Site. Byramjee-Jeejeebhoy Government Medical College. Pune, India. | pt_BR |
Affilliation | Johns Hopkins University Clinical Research Site. Byramjee-Jeejeebhoy Government Medical College. Pune, India. | pt_BR |
Affilliation | Johns Hopkins University Clinical Research Site. Byramjee-Jeejeebhoy Government Medical College. Pune, India. | pt_BR |
Affilliation | Johns Hopkins University School of Medicine. Baltimore, MD, United States. | pt_BR |
Affilliation | Rutgers- New Jersey Medical School. Center for Emerging Pathogens. Newark, NJ, United States. | pt_BR |
Affilliation | Johns Hopkins University Clinical Research Site. Byramjee-Jeejeebhoy Government Medical College. Pune, India. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Bahia, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative, Salvador, BA, Brazil. | pt_BR |
Affilliation | Rutgers- New Jersey Medical School. Center for Emerging Pathogens. Newark, NJ, United States. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Bahia, Brasil / Johns Hopkins University School of Medicine. Baltimore, MD, United States. | pt_BR |
Subject | HIV | pt_BR |
Subject | Tuberculosis | pt_BR |
Subject | Ttranscriptomics | pt_BR |
Subject | Diagnosis | pt_BR |
Subject | Gene signature | pt_BR |