Diagnostic ‘omics’ for active tuberculosis

Haas, Carolin; Roe, Jennifer; Pollara, Gabriele; Mehta, Meera; Noursadeghi, Mahdad

doi:10.1186/s12916-016-0583-9

Cited by 67 publications

(53 citation statements)

References 103 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The transcriptomic datasets for meta-analysis were chosen such that they were from (a) whole-blood expression profiles generated through microarray experiments of (b) adult TB patients, (c) and have at least a few age-matched controls in the same dataset. Although there are a few more datasets listed for tuberculosis, 16 several of them were from PBMCs and were therefore not considered to eliminate any bias due to differences in the source tissue. Those datasets that compared TB transcriptomes with other diseases, but not with healthy controls were also not considered.…”

Section: Resultsmentioning

confidence: 99%

“…16–20 An integrated analysis of insights obtained from multiple levels in the omics chain can collectively shed light on changes that are effectively translated from the genome and how they affect functions at the molecular level, thereby providing a comprehensive and integrated perspective on the myriad changes that occur upon infection, as well as on subsequent therapeutic intervention, paving the way towards personalised medicine.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Meta-analysis of host response networks identifies a common core in tuberculosis

et al. 2017

View full text Add to dashboard Cite

Tuberculosis remains a major global health challenge worldwide, causing more than a million deaths annually. To determine newer methods for detecting and combating the disease, it is necessary to characterise global host responses to infection. Several high throughput omics studies have provided a rich resource including a list of several genes differentially regulated in tuberculosis. An integrated analysis of these studies is necessary to identify a unified response to the infection. Such data integration is met with several challenges owing to platform dependency, patient heterogeneity, and variability in the extent of infection, resulting in little overlap among different datasets. Network-based approaches offer newer alternatives to integrate and compare diverse data. In this study, we describe a meta-analysis of host’s whole blood transcriptomic profiles that were integrated into a genome-scale protein–protein interaction network to generate response networks in active tuberculosis, and monitor their behaviour over treatment. We report the emergence of a highly active common core in disease, showing partial reversals upon treatment. The core comprises 380 genes in which STAT1, phospholipid scramblase 1 (PLSCR1), C1QB, OAS1, GBP2 and PSMB9 are prominent hubs. This network captures the interplay between several biological processes including pro-inflammatory responses, apoptosis, complement signalling, cytoskeletal rearrangement, and enhanced cytokine and chemokine signalling. The common core is specific to tuberculosis, and was validated on an independent dataset from an Indian cohort. A network-based approach thus enables the identification of common regulators that characterise the molecular response to infection, providing a platform-independent foundation to leverage maximum insights from available clinical data.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Meta-analysis of host response networks identifies a common core in tuberculosis

et al. 2017

View full text Add to dashboard Cite

show abstract

“…The clinical utility of metabolomics has been discussed and emphasized for multiple diseases, including car-diovascular diseases [139], obesity and Type 2 diabetes [140,141], rheumatoid arthritis and osteoarthritis [142], multiple sclerosis [143], infectious diseases [144], neurological and psychiatric diseases [145], kidney diseases [146] and cancer [147,148]. Nonetheless, among these pathologies, a very small spectrum of validated biomarkers is today used in clinical practice.…”

Section: Current Status Of Metabolomics In Clinical Applicationsmentioning

confidence: 98%

Analytical Pitfalls and Challenges in Clinical Metabolomics

et al. 2016

View full text Add to dashboard Cite

Metabolomics-based strategies have become an integral part of modern clinical research, allowing for a better understanding of pathophysiological conditions and disease mechanisms, as well as providing innovative tools for more adequate diagnostic and prognosis approaches. Metabolomics is considered an essential tool in precision medicine, which aims for personalized prevention and tailor-made treatments. Nevertheless, multiple pitfalls may be encountered in clinical metabolomics during the entire workflow, hampering the quality of the data and, thus, the biological interpretation. This review describes the challenges underlying metabolomics-based experiments, discussing step by step the potential pitfalls of the analytical process, including study design, sample collection, storage, as well as preparation, chromatographic and electrophoretic separation, detection and data analysis. Moreover, it offers practical solutions and strategies to tackle these challenges, ensuring the generation of high-quality data.

show abstract

“…The aim is to improve sensitivity, speed, ease of use, ability to discriminate TB from other inflammatory or autoimmune diseases and identify subclinical TB in HIV infection [102]. However, very few candidate assays are in the R&D pipeline for true point-of-care tests in RDT format, with disappointing results from biomarker research [103].…”

Section: Futurementioning

confidence: 99%

Diagnosis of opportunistic infections

Scott

Silva

Boehme

et al. 2017

Current Opinion in HIV and AIDS

View full text Add to dashboard Cite

Purpose of the review TB incidence has declined ~1.5% annually since 2000, but continued to affect 10.4 million individuals in 2015, with 1/3 remaining undiagnosed or under reported. The diagnosis of TB among those co-infected with HIV is challenging as TB remains the leading cause of death in such individuals. Accurate and rapid diagnosis of active TB will avert mortality in both adults and children, reduce transmission, and assist in timeous decisions for ART initiation. This review describes advances in diagnosing TB, especially among HIV co-infected individuals, highlights national program’s uptake, and impact on patient care. Recent Findings The TB diagnostic landscape has been transformed over the last 5 years. Molecular diagnostics such as Xpert MTB/RIF, which simultaneously detects M. tuberculosis resistance to rifampicin, has revolutionised TB control programs. WHO endorsed the use of Xpert MTB/RIF in 2010 for use in HIV/TB co-infected patients, and later in 2013 for use as the initial diagnostic test for all adults and children with signs and symptoms of pulmonary TB. Line probe assays (LPAs) are recommended for the detection of rifampicin and isoniazid resistance in sputum smear-positive specimens and mycobacterial cultures. A second-line line probe assay has been recommended for the diagnosis of extensively drug-resistant (XDR)-TB Assays such as the urine lateral flow(LF)-lipoarabinomannan(LAM), can be used at the point of care (POC) and have a niche role to supplement the diagnosis of TB in seriously ill HIV infected, hospitalized patients with low CD4<100cells/μl. Polyvalent platforms such as the m2000 (Abbott Molecular, IL, USA) and GeneXpert (Cepheid, CA, USA) offer potential for integration of HIV and TB testing services. While the Research and Development (R&D) pipeline appears to be rich at first glance, there are actually few leads for true POC tests that would allow for earlier TB diagnosis or rapid, comprehensive drug susceptibility testing, especially when considering the very high attrition rates observed between biomarker discovery and product market entry. Summary In this review, we describe diagnostic strategies specifically for HIV and TB co-infected individuals. Molecular diagnostics in particular within the past 5 years have revolutionized and “disrupted” this field. They lend themselves to integration of services with platforms capable of polyvalent testing. Impact on patient care is, however, still debatable. What has been highlighted is the need for health system strengthening and for true POC testing that can be used in active case finding.

show abstract

Diagnostic ‘omics’ for active tuberculosis

Cited by 67 publications

References 103 publications

Meta-analysis of host response networks identifies a common core in tuberculosis

Meta-analysis of host response networks identifies a common core in tuberculosis

Analytical Pitfalls and Challenges in Clinical Metabolomics

Diagnosis of opportunistic infections

Contact Info

Product

Resources

About