scholarly journals Heme Oxygenase-1 and Neopterin Plasma/Serum Levels and their role in Diagnosing Active and Latent TB among HIV/TB Co-Infected Patients

2019 ◽  
Author(s):  
Uwimaana Esther ◽  
Bernard S Bagaya ◽  
Barbara Castelnuovo ◽  
David P Kateete ◽  
Anguzu Godwin ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Heme Oxygenase ◽  
Area Under The Curve ◽  
Serum Levels ◽  
Diagnostic Tools ◽  
Heme Oxygenase 1 ◽  
Hiv Patients ◽  
Receiver Operating Characteristic Curves ◽  
Latent Tb ◽  
Latent Tb Infection

Abstract Background: Tuberculosis(TB) diagnosis in the presence of HIV co-infection remains challenging. Heme oxygenase 1(HO-1) and neopterin have been validated as potential biomarkers for TB diagnosis. Infection of macrophages with Mycobacterium tuberculosis (M .tb ) causes the production of HO-1 and neopterin and previous studies have shown these to be markers of immune activation. This study was conducted to determine the levels of HO-1 and neopterin and their utility in the diagnosis of TB among individuals enrolled in the Community Health and Social Network of Tuberculosis(COHSONET) study and the Kampala TB Drug Resistance Survey(KDRS). Methods: A total of 210 participants were enrolled in a study of a diagnostic method aimed at determining the levels of HO-1 and neopterin and determine their diagnostic accuracy as biomarkers in TB diagnosis from March to May 2019. M. tb culture was performed on sputum to confirm active TB(ATB) and QuantiFERON TB gold test to confirm latent TB infection(LTBI). ELISAs were performed to determine the levels of HO-1 and neopterin. Data analysis was done using Kruskal Wallis and Receiver Operating Characteristic curves to determine the diagnostic accuracy. Results: HO-1 levels among ATB/HIV patients, LTBI/HIV patients and TB negative individuals were 10.7ng/ml (IQR: 7.3-12.7ng/ml), 7.5ng/ml (IQR: 5.4-14.1ng/ml), 3.3ng/ml (IQR: 2.0-7.1ng/ml) respectively. Neopterin levels among ATB/HIV patients, LTBI/HIV patients and TB negative individuals were 11.7ng/ml (IQR: 5.219.4ng/ml), 8.8ng/ml (IQR: 2.4-19.8ng/ml), and 5.9ng/ml (IQR: 3.410.2ng/ml) respectively. HO-1 showed a sensitivity of 78.57% and a specificity of 71.43% with area under the curve(AUC) of 0.839 when used to diagnose ATB. HO-1 showed AUC of 0.79, sensitivity of 70% and specificity 70% when used to diagnose LTB. Neopterin showed a sensitivity of 61.43% and a specificity of 74.29% with AUC 0.71 when used to diagnose ATB. Neopterin as a biomarker in LTB diagnosis showed AUC of 0.56 which was not significant. Conclusion: HO-1 and neopterin are valuable diagnostic biomarkers for ATB and LTB which could be further utilized to develop less costly rapid diagnostic tools to overcome current TB diagnostic challenges.

scholarly journals Heme oxygenase-1 and neopterin plasma/serum levels and their role in diagnosing active and latent TB among HIV/TB co-infected patients: a cross sectional study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Esther Uwimaana ◽  
Bernard S. Bagaya ◽  
Barbara Castelnuovo ◽  
David P. Kateete ◽  
Anguzu Godwin ◽  
...  
Keyword(s):  
Heme Oxygenase ◽  
Cross Sectional Study ◽  
Hiv Positive ◽  
Heme Oxygenase 1 ◽  
Sectional Study ◽  
Serum Samples ◽  
Cross Sectional ◽  
Significant Difference ◽  
Latent Tb ◽  
Latent Tb Infection

Abstract Background Tuberculosis (TB) diagnosis in the context of HIV co-infection remains challenging. Heme oxygenase 1 (HO-1) and neopterin have been validated as potential biomarkers for TB diagnosis. Latent TB infection (LTBI) is diagnosed using tuberculin skin test (TST) and interferon gamma release assays (T-Spot and QuantiFERON TB gold tests, respectively). However, these tests have shown challenges and yet diagnosing LTBI is important for the overall control of TB. This study was conducted to determine the levels of H0–1 and neopterin, and their role in the diagnosis of TB among individuals enrolled in the Community Health and Social Network of Tuberculosis (COHSONET) study and the Kampala TB Drug Resistance Survey (KDRS). Methods This was a nested cross-sectional study. Plasma and serum samples collected from 140 patients at Mulago National Referral Hospital, Kampala Uganda were used. M.tb culture was performed on sputum to confirm active TB(ATB) and QuantiFERON TB gold test to confirm latent TB infection (LTBI). ELISAs were performed to determine the levels of HO-1 and neopterin. Data analysis was done using t-test and Receiver Operating Characteristic curves to determine the diagnostic accuracy. Results HO-1 levels among active tuberculosis (ATB)/HIV-infected patients and LTBI/HIV-infected patients were 10.7 ng/ml (IQR: 7.3–12.7 ng/ml) and 7.5 ng/ml (IQR: 5.4–14.1 ng/ml) respectively. Neopterin levels among ATB/HIV-positive patients and LTBI/HIV-positive patients were 11.7 ng/ml (IQR: 5.2.4 ng/ml) and 8.8 ng/ml (IQR: 2.4–19.8 ng/ml), respectively. HO-1 showed a sensitivity of 58.57% and a specificity of 67.14% with area under the curve (AUC) of 0.57 when used to discriminate between ATB and LTB. Neopterin showed an AUC of 0.62 with a sensitivity of 57.14% and a specificity of 60.0% when used to distinguish ATB from LTB. Conclusion There was no in significant difference in HO-1 concentration levels of ATB individuals compared to LTB individuals. There was a significant difference in neopterin concentrations levels of ATB individuals compared to latently infected individuals. Findings from this study, show that HO-1 and neopterin have poor ability to distinguish between ATB and LTB.

scholarly journals Diagnostic accuracy of combinations of serological biomarkers for identifying clinical tuberculosis

2018 ◽  
Vol 12 (06) ◽  
pp. 429-441 ◽  
Author(s):  
Zaida Araujo ◽  
Noe Macias-Segura ◽  
Juan Ernesto Lopez-Ramos ◽  
Jacobus Henry De Waard ◽  
Magnolia Vanegas ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Roc Analysis ◽  
Target Population ◽  
Diagnostic Tools ◽  
Receiver Operator Curve ◽  
Discriminative Ability ◽  
Latent Tb ◽  
Latent Tb Infection ◽  
Serological Biomarkers ◽  
Operator Curve

Introduction: Confirmation of tuberculosis (TB) cases in endemic TB settings is a challenge; obtaining fast and cheap, though accurate, diagnostic tools such as biomarkers is thus urgently needed to enable the early detection of TB. This paper evaluates the diagnostic accuracy of combinations of host serological biomarkers for identifying TB. Methodology: Enzyme-linked immunosorbent assays (ELISA) were used on 70 Venezuelan Creole individuals for evaluating host biomarkers (i.e. CXCL9, sCD14, MMP9 and uPAR proteins) and anti-synthetic peptides covering certain Mycobacterium tuberculosis (Mtb) ESAT-6 (P-12033, P-12034 and P-12037) and Ag85A (P-29878) antigen sequences. The target population consisted of adults having active TB (ATB, n = 28), the tuberculin skin test positive (TST+) or individuals with latent TB infection (LTB, n = 28) and TST- or control subjects (CTRL, n = 14). Results: Receiver operator curve (ROC) analysis revealed good biosignature discriminative ability for 5 serological biomarkers; the accuracy of 3 combinations had a good discriminative ability for diagnosing TB. Anti-P-12034/uPAR detected TB with 96.7% sensitivity and 86.0% specificity, followed by anti-P-12033/uPAR having 96.7% sensitivity and 81.4% specificity. Anti-P-29878/MMP9 had the highest sensitivity (100%), but low specificity (52.17%). Biomarker combinations did not prove efficacious for identifying incipient subclinical TST+TB− subjects at high-risk for TB. Conclusions: The anti-P-12034/uPAR combination could be useful for identifying clinical TB patients. Such an approach holds promise for further validation.

scholarly journals Cytokine Biosignature of Active and Latent Mycobacterium Tuberculosis Infection in Children

Pathogens ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 517
Author(s):  
Magdalena Druszczynska ◽  
Michal Seweryn ◽  
Sebastian Wawrocki ◽  
Magdalena Kowalewska-Pietrzak ◽  
Anna Pankowska ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Inflammatory Mediators ◽  
Latent Tuberculosis ◽  
Serum Levels ◽  
Diagnostic Tools ◽  
Mycobacterium Tuberculosis Infection ◽  
Only Children ◽  
Latent Tb ◽  
Ifn Γ ◽  
Multiplex Bead

None of the currently used diagnostic tools are efficient enough in diagnosing Mycobacterium tuberculosis (M.tb) infection in children. The study was aimed to identify cytokine biosignatures characterizing active and latent tuberculosis (TB) in children. Using a multiplex bead-based technology, we analyzed the levels of 53 Th17-related cytokines and inflammatory mediators in sera from 216 BCG-vaccinated children diagnosed with active TB (TB) or latent TB (LTBI) as well as uninfected controls (HC). Children with active TB, compared to HC children, showed reduced serum levels of IL-17A, MMP-2, OPN, PTX-3, and markedly elevated concentrations of APRIL/TNFSF13. IL-21, sCD40L, MMP-2, and IL-8 were significantly differentially expressed in the comparisons between groups: (1) HC versus TB and LTBI (jointly), and (2) TB versus LTBI. The panel consisting of APRIL/TNFSF13, sCD30/TNFRSF8, IFN-α2, IFN-γ, IL-2, sIL-6Rα, IL-8, IL-11, IL-29/IFN-λ1, LIGHT/TNFSF14, MMP-1, MMP-2, MMP-3, osteocalcin, osteopontin, TSLP, and TWEAK/TNFSF12 possessed a discriminatory potential for the differentiation between TB and LTBI children. Serum-based host biosignatures carry the potential to aid the diagnosis of childhood M.tb infections. The proposed panels of markers allow distinguishing not only children infected with M.tb from uninfected individuals but also children with active TB from those with latent TB.

The Association of PSA-IGM and Total PSA Improves the Diagnosis of Prostate Cancer

2009 ◽  
Vol 24 (3) ◽  
pp. 212-212
Author(s):  
Danilo Zani ◽  
Silvia Costa ◽  
Lorenzo Gatti ◽  
Nicola Pesenti ◽  
Alberto Pettenò ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Diagnostic Accuracy ◽  
Prostate Biopsy ◽  
Specific Antigen ◽  
Digital Rectal Examination ◽  
Serum Levels ◽  
Immunoglobulin M ◽  
Diagnostic Tools ◽  
Psa Test ◽  
Total Psa

Background and aim The specific causes of prostate cancer (Pca) are unknown but the main risk factors of tumor development are associated with age, genetic factors, ethnicity, diet and lifestyle. Prostate cancer is rare in men under 45 years of age, but becomes more common with advancing age. The main diagnostic tools for demonstrating the presence of PCa include digital rectal examination, transrectal ultrasonography, and serum measurement of prostate specific antigen (PSA) followed by prostate biopsy for confirmation of the diagnosis. While the measurement of PSA levels has revolutionized the diagnosis of PCa, it has also increased its overdiagnosis due to the poor diagnostic accuracy. Scientific evidence indicates that biomarkers for different types of cancer such as liver and colorectal cancer circulate in the blood associated with immunoglobulin M (IgM) to form complexes that allow a better diagnosis in comparison to circulating free biomarkers. In prostate cancer it has been demonstrated that testing for serum levels of the PSA-IgM immune complex improves the diagnostic performance of total PSA. The aim of this study was to evaluate the diagnostic accuracy of PSA-IgM compared to total PSA for the selection of patients to be submitted to transrectal ultrasound-guided prostate biopsy. Patients and methods Serum samples from 67 male patients, 33 affected by PCa with a Gleason score from 5 to 7, and 34 affected by benign prostate hypertrophy (BPH), were collected by the Department of Urology of the Spedali Civili of Brescia. The samples were immediately snap frozen at −80°C. Serum levels of PSA-IgM were assessed using Prostate-IC (Xeptagen, Italy) while PSA levels were determined with the Immulite 2000 of Medical Systems S.p.A. Results Patients were stratified into 2 groups according to age; the first group consisted of 24 patients with PCa and 20 with BPH aged between 60 and 70 years and the second group consisted of 9 patients with PCa and 14 with BPH aged between 70 and 80 years. Serum levels of PSA and PSA-IgM were analyzed in the 2 groups using cutoff values of 4 ng/mL for PSA and 145 AU/mL for PSA-IgM. In the first group, 1 8 of 24 PCa patients were positive for PSA (75% sensitivity) with a specificity of 50% (10 of 20 BPH patients), and 1 0 of 24 PCa patients were positive with the PSA-IgM assay (42% sensitivity), which had a higher specificity (70%; 6 of 20 BPH patients). The combination of both biomarkers resulted in a sensitivity of 38% (9 of 24 patients with PCa) but showed a significant improvement in specificity up to 90%, since 18 of 20 patients with BPH were negative for at least one test. In the second group of patients aged 70 to 80 years, the PSA test had a sensitivity of 67% (6/9 PCa patients) and a specificity of 78% (3/14 BPH patients) compared with a sensitivity of 44% for the PSA-IgM test (4/9 PCa patients) with a specificity of 71% (4/14 BPH patients). The combination of PSA and PSA-IgM had a sensitivity of 30% (3/9) but the highest specificity (93%, 13/14 BPH patients). Conclusion The results of the study demonstrate the diagnostic value of the PSA-IgM assay compared with the total PSA test. The combination of PSA-IgM with total PSA was the best approach to reduce the number of false-positive results, thus improving the diagnosis of prostate cancer.

Decidual expression and maternal serum levels of heme oxygenase 1 are increased in pre-eclampsia

2008 ◽  
Vol 87 (3) ◽  
pp. 272-279 ◽  
Author(s):  
Irina P. Eide ◽  
Christina V. Isaksen ◽  
Kjell Å. Salvesen ◽  
Mette Langaas ◽  
Svanhild A. Schønberg ◽  
...  
Keyword(s):  
Heme Oxygenase ◽  
Serum Levels ◽  
Maternal Serum ◽  
Heme Oxygenase 1

scholarly journals Translation of a Circulating microRNA Signature of Melanoma to a Novel Solid-Tissue Biomarker to Improve Diagnostic Accuracy and Reproducibility.

2021 ◽  
Author(s):  
Ryan Van Laar ◽  
Samuel King ◽  
Richard McCoy ◽  
Mirette Saad ◽  
Sian Fereday ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Intraclass Correlation ◽  
Area Under The Curve ◽  
Digital Gene Expression ◽  
Disease Status ◽  
Skin Lesions ◽  
Disease Stage ◽  
Diagnostic Tools ◽  
Routine Practice ◽  
Circulating Microrna

Abstract Background Successful treatment of cutaneous melanoma depends on early and accurate diagnosis of clinically suspicious melanocytic skin lesions. Currently, histopathology examination of excised skin lesions is considered the ‘gold standard’ for diagnosis of melanoma. Multiple studies have shown the low accuracy and reproducibility of this method, underscoring the urgent need for new diagnostic tools, including disease-specific biomarkers. Previously, a 38-microRNA signature of melanoma (‘Mel38’) was previously identified in plasma and validated as novel circulating biomarker. In this study, Mel38 expression in solid biopsy tissue is examined to determine its ability to contribute to accurate and reproducible melanoma diagnoses.Methods Nanostring digital gene expression profiling was used to apply the Mel38 signature in a cohort of 308 formalin fixed paraffin embedded skin biopsies (‘Mel38’). Genomic data were interrogated using hierarchical clustering, univariate and multivariate statistical approaches. Mel38 classification scores (range 0 to 10) were compared to consensus histopathology results, including MPATH-DX class, AJCC disease stage, histological subtype as well as technical assay factors.Results The Mel38 score can identify high-risk melanomas (MPATH-Dx Class IV) from less-malignant forms of the disease with an area-under-the curve of 0.96 (P < 0.001). The genomic score ranges from 0 to 10 and is positively correlated with the melanoma progression, from benign naevi to metastatic disease (intraclass correlation coefficient: 0.85). Using a score threshold of > 2.3 identifies higher-risk melanomas, associated with poorer outcomes and more intensive suggested clinical actions. Multivariate analysis showed the score to be a significant predictor of malignancy, independent of technical and clinical covariates. Analysis of the Mel38 signature in spitz naevi reveal an intra-subtype profile, in common to both benign and malignant conditions.Conclusion Melanoma-specific circulating microRNAs maintain their association with malignancy when measured in the hypothesized tissue of origin. The Mel38 signature is an accurate and reproducible metric of melanoma status, based on changes in microRNA expression that occur as the disease develops and spreads. Inclusion of the Mel38 score into routine practice would give physicians a genomic assessment of a patient’s disease status. Combining molecular biomarker data with conventional histopathology data may improve diagnostic accuracy, reproducibility, and patient outcomes.

Clinical Application of Two-Dimensional Scanning Digital Kymography in Discrimination of Diplophonia

2019 ◽  
Vol 62 (10) ◽  
pp. 3643-3654
Author(s):  
In-Ho Bae ◽  
Soo-Geun Wang ◽  
Soon-Bok Kwon ◽  
Seong-Tae Kim ◽  
Eui-Suk Sung ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Confusion Matrix ◽  
Muscle Tension ◽  
Area Under The Curve ◽  
Diagnostic Methods ◽  
Waveform Analysis ◽  
Perceptual Judgment ◽  
Diagnostic Tools ◽  
Perceptual Evaluation ◽  
Time Required

Purpose The purpose of this study was to investigate the characteristics of diplophonia using an auditory perception and multimodal simultaneous examination, which included sound waveform analysis, electroglottography (EGG), digital kymography (DKG), and 2-dimensional scanning digital kymography (2D DKG). Additionally, we compared the diagnostic accuracy of each method using a binary classifier in confusion matrix and convenience of discrimination, based on the time required for interpretation. Method One normophonic male, 12 patients with diplophonia, and 12 dysphonia patients without diplophonia were enrolled. A multimodal simultaneous evaluation was used to analyze the vibration pattern of diplophonia. Sensitivity, specificity, accuracy, area under the curve, and interpretation time were used to compare the various diagnostic methods. Discrimination was determined by 3 raters. Results There are 3 types of asymmetric vibratory patterns in diplophonia. The types are based on the oscillators vibrating at different frequencies: asymmetry of the left and right cords (6 subjects with unilateral palsy and 1 subject with vocal polyps), asymmetry of anterior and posterior cords (2 subjects with vocal polyps), and asymmetry of true and false cords (3 subjects with muscle tension dysphonia). All evaluation methods were useful as diagnostic tools, with all areas under the curve > .70. The diagnostic accuracy was highest with DKG (95.83%), followed by 2D DKG (83.33%), EGG (81.94%), auditory-perceptual evaluation (80.56%), and sound waveform (77.78%). The interpretation time was the shortest for auditory-perceptual evaluation (6.07 ± 1.34 s), followed by 2D DKG (10.04 ± 3.00 s), EGG (12.49 ± 2.76 s), and DKG (13.53 ± 2.60 s). Conclusions Auditory-perceptual judgment was the easiest and fastest method for experienced raters, but its diagnostic accuracy was lower than that of DKG or 2D DKG. The diagnostic accuracy of DKG was the highest, but 2D DKG allowed rapid interpretation and showed relatively high diagnostic accuracy, except in cases with space-occupying lesions. Supplemental Material https://doi.org/10.23641/asha.9911786

Unnoticed Adverse Effect of Isoniazid during Childhood Tuberculosis Preventive Treatment: Hyperuricemia

2021 ◽  
Author(s):  
Bahar Kandemir ◽  
Ipek Duman ◽  
Yasemin Durduran ◽  
Ozge Metin Akcan ◽  
Muhammed Burak Selver ◽  
...  
Keyword(s):  
Uric Acid ◽  
Median Duration ◽  
Preventive Treatment ◽  
Serum Levels ◽  
Positive Tuberculin Skin Test ◽  
University Hospital ◽  
Latent Tb ◽  
Latent Tb Infection ◽  
Elevated Transaminases

Abstract Objective Isoniazid for 6 to 9 months is the most widely used form of tuberculosis (TB) preventive treatment. We aimed to assess the adverse effects of isoniazid by using the serum levels of aspartate transaminase (AST), alanine transaminase (ALT), and uric acid (SUA) in children and adolescents receiving long-term isoniazid for latent TB infection. Methods The study included children ≤18 years of age who underwent TB preventive treatment with isoniazid (IPT) between 2015 and 2019 at a university hospital. Serum transaminase, SUA, urea, and creatinine levels of patients were measured before the initiation of IPT, 15th day, and once a month during treatment. Patients with ALT, AST, or SUA results above cut-off levels during treatment were evaluated. The final values in follow-up were included in the data analysis. Results A total of 141 children who underwent IPT were included. In total, 70 children had family members with confirmed TB disease, and 71 children had a positive tuberculin skin test. SUA increased above cut-off values in 16 children (11.3%), and half of them had uric acid levels over 7 mg/dL. The median duration of the development of hyperuricemia was 4.0 months. ALT or AST increased above cut-off values in 23 children (16.3%). ALT was above cut-off values in seven patients, AST was high in 20 patients. The median duration to the development of AST and/or ALT levels above cut-off was 4.0 months. Two patients had hepatotoxic transaminase levels. Three patients had both elevated transaminases and SUA levels. Conclusion Isoniazid may also cause hyperuricemia besides elevation in transaminases in children.

scholarly journals Serum Heme Oxygenase-1 and BMP-7 Are Potential Biomarkers for Bone Metabolism in Patients with Rheumatoid Arthritis and Ankylosing Spondylitis

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Tong-ling Yuan ◽  
Jin Chen ◽  
Yan-li Tong ◽  
Yan Zhang ◽  
Yuan-yuan Liu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Ankylosing Spondylitis ◽  
Bone Metabolism ◽  
Bone Remodeling ◽  
Heme Oxygenase ◽  
Serum Levels ◽  
Heme Oxygenase 1 ◽  
Tartrate Resistant Acid Phosphatase ◽  
Trap 5B ◽  
Potential Biomarkers

Backgrounds. Heme oxygenase-1 (HO-1) has been reported to play a regulatory role in osteoclastogenesis. Bone morphogenetic protein (BMP) pathways induce osteoblastic differentiation and bone remodeling.Aims. To identify serum levels of HO-1, BMP-7, and Runt related-transcription factor 2 (Runx2) in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) and to investigate the relationships between HO-1, BMP-7, Runx2, and other common biomarkers for bone metabolism.Results. Serum levels of HO-1 and BMP-7 were revealed to be significantly higher in patients with RA or AS than in healthy controls (p<0.01). In RA group, HO-1 was positively correlated with BMP-7, Runx2, and tartrate-resistant acid phosphatase-5b (TRAP-5b) (p<0.05, resp.), BMP-7 was positively correlated with Runx2 and TRAP-5b (p<0.05, resp.), and Runx2 was negatively correlated with N-terminal midfragment of osteocalcin (NMID) (p<0.05). In AS group, we observed identical correlation between HO-1 and BMP-7, but opposite correlations between BMP-7 and TRAP-5b and between Runx2 and NMID, when comparing with the RA cohort.Conclusion. Our findings suggest that HO-1 and BMP-7 are potential biomarkers for bone metabolism in patients with RA and AS. The different correlations between the bone markers point to distinct differences in bone remodeling pathways in the two types of arthritis.

scholarly journals Comparing tuberculosis gene signatures in malnourished individuals using the TBSignatureProfiler

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
W. Evan Johnson ◽  
Aubrey Odom ◽  
Chelsie Cintron ◽  
Mutharaj Muthaiah ◽  
Selby Knudsen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Sequencing ◽  
Area Under The Curve ◽  
Severe Malnutrition ◽  
Gene Set ◽  
Gene Sets ◽  
Z Scores ◽  
Latent Tb ◽  
Latent Tb Infection ◽  
User Friendly

Abstract Background Gene expression signatures have been used as biomarkers of tuberculosis (TB) risk and outcomes. Platforms are needed to simplify access to these signatures and determine their validity in the setting of comorbidities. We developed a computational profiling platform of TB signature gene sets and characterized the diagnostic ability of existing signature gene sets to differentiate active TB from LTBI in the setting of malnutrition. Methods We curated 45 existing TB-related signature gene sets and developed our TBSignatureProfiler software toolkit that estimates gene set activity using multiple enrichment methods and allows visualization of single- and multi-pathway results. The TBSignatureProfiler software is available through Bioconductor and on GitHub. For evaluation in malnutrition, we used whole blood gene expression profiling from 23 severely malnourished Indian individuals with TB and 15 severely malnourished household contacts with latent TB infection (LTBI). Severe malnutrition was defined as body mass index (BMI) < 16 kg/m2 in adults and based on weight-for-height Z scores in children < 18 years. Gene expression was measured using RNA-sequencing. Results The comparison and visualization functions from the TBSignatureProfiler showed that TB gene sets performed well in malnourished individuals; 40 gene sets had statistically significant discriminative power for differentiating TB from LTBI, with area under the curve ranging from 0.662–0.989. Three gene sets were not significantly predictive. Conclusion Our TBSignatureProfiler is a highly effective and user-friendly platform for applying and comparing published TB signature gene sets. Using this platform, we found that existing gene sets for TB function effectively in the setting of malnutrition, although differences in gene set applicability exist. RNA-sequencing gene sets should consider comorbidities and potential effects on diagnostic performance.

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