The QuantiFERON-TB Gold Plus (QFT-Plus; Qiagen, Germantown, MD) interferon gamma release assay (IGRA) received FDA clearance in 2017 and will replace the prior version of the assay, the QFT-Gold In-Tube (QFT-GIT). Here, we compared performances of the QFT-Plus assay and the QFT-GIT version in a diverse patient population, including patients undergoing evaluation for or follow-up of latent tuberculosis infection (LTBI; = 39) or active TB infection ( = 3), and in health care workers (HCWs; = 119) at Mayo Clinic (Rochester, MN). Compared to the QFT-GIT, the QFT-Plus assay showed 91.2% (31/34) positive, 98.4% (124/126) negative, and 96.6% (156/161) overall qualitative agreement among the 161 enrolled subjects, with a Cohen's kappa value of 0.91 (excellent interrater agreement). Among the 28 patients diagnosed with LTBI at the time of enrollment, the QFT-GIT and QFT-Plus assays agreed in 24 (85.7%) patients; in all four discordant patients, the positivity of the QFT-GIT or QFT-Plus IGRA was associated with low-level interferon gamma (IFN-γ) reactivity, ranging from 0.36 IU/ml to 0.66 IU/ml. Additionally, we document a high degree of correlation between IFN-γ levels in the QFT-GIT TB antigen tube and each of the two QFT-Plus TB antigen tubes, as well as between the QFT-Plus TB1 and TB2 tubes (Pearson's correlation coefficients [] > 0.95). Overall, we show comparable results between the QFT-GIT and QFT-Plus assays in our study population composed of subjects presenting with a diverse spectrum of TB infections. Our findings suggest that the necessary transition to the QFT-Plus assay will be associated with a minimal difference in assay performance characteristics.

Literature-based discovery (LBD) summarizes information and generates insight from large text corpuses. The SemNet framework utilizes a large heterogeneous information network or “knowledge graph” of nodes and edges to compute relatedness and rank concepts pertinent to a user-specified target. SemNet provides a way to perform multi-factorial and multi-scalar analysis of complex disease etiology and therapeutic identification using the 33+ million articles in PubMed. The present work improves the efficacy and efficiency of LBD for end users by augmenting SemNet to create SemNet 2.0. A custom Python data structure replaced reliance on Neo4j to improve knowledge graph query times by several orders of magnitude. Additionally, two randomized algorithms were built to optimize the HeteSim metric calculation for computing metapath similarity. The unsupervised learning algorithm for rank aggregation (ULARA), which ranks concepts with respect to the user-specified target, was reconstructed using derived mathematical proofs of correctness and probabilistic performance guarantees for optimization. The upgraded ULARA is generalizable to other rank aggregation problems outside of SemNet. In summary, SemNet 2.0 is a comprehensive open-source software for significantly faster, more effective, and user-friendly means of automated biomedical LBD. An example case is performed to rank relationships between Alzheimer’s disease and metabolic co-morbidities.

Rationale: Most immunocompetent patients diagnosed with latent tuberculosis infection (LTBI) will not progress to tuberculosis (TB) reactivation. However, current diagnostic tools cannot reliably distinguish nonprogressing from progressing patients a priori, and thus LTBI therapy must be prescribed with suboptimal patient specificity. We hypothesized that LTBI diagnostics could be improved by generating immunomarker profiles capable of categorizing distinct patient subsets by a combinatorial immunoassay approach.Objectives: A combinatorial immunoassay analysis was applied to identify potential immunomarker combinations that distinguish among unexposed subjects, untreated patients with LTBI, and treated patients with LTBI and to differentiate risk of reactivation.Methods: IFN-g release assay (IGRA) was combined with a flow cytometric assay that detects induction of CD25 1 CD134 1 coexpression on TB antigen-stimulated T cells from peripheral blood. The combinatorial immunoassay analysis was based on receiver operating characteristic curves, technical cut-offs, 95% bivariate normal density ellipse prediction, and statistical analysis. Risk of reactivation was estimated with a prediction formula.Measurements and Main Results: Sixty-five out of 150 subjects were included. The combinatorial immunoassay approach identified at least four different T-cell subsets. The representation of these immune phenotypes was more heterogeneous in untreated patients with LTBI than in treated patients with LTBI or unexposed groups. Patients with IGRA(1) CD41 CD25 1 CD134 1 T-cell phenotypes had the highest estimated reactivation risk (4.11 6 2.11%).Conclusions: These findings suggest that immune phenotypes defined by combinatorial assays may potentially have a role in identifying those at risk of developing TB; this potential role is supported by risk of reactivation modeling. Prospective studies will be needed to test this novel approach.

Bronchoscopy provided diagnostic confirmation of pulmonary TB in 10% of subjects at least 2 negative induced-sputum samples by smear microscopy and NAA testing.