Development and Validation of Plasma miRNA Biomarker Signature Panel for the Detection of Early HIV-1 Infection

2018 ◽  
Author(s):  
Santanu Biswas ◽  
Mohan Haleyurgirisetty ◽  
Sherwin Lee ◽  
Indira Hewlett ◽  
Krishnakumar Devadas
EBioMedicine ◽  
2019 ◽  
Vol 43 ◽  
pp. 307-316 ◽  
Author(s):  
Santanu Biswas ◽  
Mohan Haleyurgirisetty ◽  
Sherwin Lee ◽  
Indira Hewlett ◽  
Krishnakumar Devadas

2017 ◽  
Vol 17 (1) ◽  
Author(s):  
Maartje Dijkstra ◽  
Godelieve J. de Bree ◽  
Ineke G. Stolte ◽  
Udi Davidovich ◽  
Eduard J. Sanders ◽  
...  

2018 ◽  
Author(s):  
Jasper C Ho ◽  
Garway T Ng ◽  
Mathias Renaud ◽  
Art FY Poon

AbstractGenotypic resistance interpretation systems for the prediction and interpretation of HIV-1 antiretroviral resistance are an important part of the clinical management of HIV-1 infection. Current interpretation systems are generally hosted on remote webservers that enable clinical laboratories to generate resistance predictions easily and quickly from patient HIV-1 sequences encoding the primary targets of modern antiretroviral therapy. However they also potentially compromise a health provider’s ethical, professional, and legal obligations to data security, patient information confidentiality, and data provenance. Furthermore, reliance on web-based algorithms makes the clinical management of HIV-1 dependent on a network connection. Here, we describe the development and validation of sierra-local, an open-source implementation of the Stanford HIVdb genotypic resistance interpretation system for local execution, which aims to resolve the ethical, legal, and infrastructure issues associated with remote computing. This package reproduces the HIV-1 resistance scoring by the web-based Stanford HIVdb algorithm with a high degree of concordance (99.997%) and a higher level of performance than current methods of accessing HIVdb programmatically.


2017 ◽  
Vol 17 (1) ◽  
Author(s):  
Maartje Dijkstra ◽  
Godelieve J. de Bree ◽  
Ineke G. Stolte ◽  
Udi Davidovich ◽  
Eduard J. Sanders ◽  
...  

2013 ◽  
Vol 193 (1) ◽  
pp. 85-95 ◽  
Author(s):  
Sonia Gutiérrez-Granados ◽  
Laura Cervera ◽  
Francesc Gòdia ◽  
Jorge Carrillo ◽  
María Mercedes Segura

2012 ◽  
Vol 30 (30_suppl) ◽  
pp. 40-40
Author(s):  
Nicholas Erho ◽  
Ismael A. Vergara ◽  
Christine Buerki ◽  
Mercedeh Ghadessi ◽  
Anamaria Crisan ◽  
...  

40 Background: Gleason score (GS) is the most widely used grading system of cell differentiation in prostate cancer and one of the best pathological predictors of disease progression. Patients with high GS (> 7) are the most likely to experience metastasis, whereas patients with low GS (< 7) are expected to have favorable long-term outcomes. In addition to the subjective nature of GS assessment, patients with GS 7 represent a heterogeneous group in terms of patient outcomes. In this study a biomarker signature is developed and validated which could improve the prediction of high risk disease among GS 7 radical prostatectomy (RP) patients. Methods: Patient specimens from the Mayo Clinic RP Registry (n = 764) were used for feature selection and training of a 392-feature K-nearest neighbor (KNN, k = 11) classifier. These 392 genomic features were identified by assessing differential expression between patients with GS < 7 and those with GS > 7, using a Bonferroni adjusted T-Test with a p-value threshold of 0.05. The classifier was subsequently validated in two independent patient cohorts (Memorial Sloan Kettering [MSKCC] and German Cancer Research Center [DKFZ]) and compared to a state of the art biomarker signature (Penney et al. 2011). Results: In the MSKCC dataset (GSE21034) our model segregated GS < 7 from GS > 7 patients (n = 56) with an area under the receiver operating characteristic curve (AUC) of 0.97, comparable to the AUC of 0.94 obtained by Penney et al. in their independent validation set (n = 45). Strong performance was observed by our model when discriminating between primary Gleason grade (pGG) 3 and pGG 4 & 5 patients in the MSKCC (n = 130) and DKFZ prostate cancer (GSE29079, n = 47) datasets, achieving AUCs of 0.75 and 0.87, respectively. In the challenging GS 7 subset, our model segregated GS 3 + 4 and 4 + 3 patients in the DKFZ dataset (n = 64) with an AUC of 0.81 outperforming the Penney et al. signature (AUC = 0.60). Conclusions: A biomarker signature was developed which discriminates between low and high GS patients, outperforming a previously reported signature. Further validation of this biomarker signature in additional post RP patients, as well as, pretreatment biopsy specimens is warranted.


2019 ◽  
Vol 466 ◽  
pp. 47-51 ◽  
Author(s):  
L.M. Kranz ◽  
B. Gärtner ◽  
A. Michel ◽  
M. Pawlita ◽  
T. Waterboer ◽  
...  

2019 ◽  
Vol 71 (10) ◽  
pp. 2645-2654 ◽  
Author(s):  
Yukari C Manabe ◽  
Bruno B Andrade ◽  
Nikhil Gupte ◽  
Samantha Leong ◽  
Manisha Kintali ◽  
...  

Abstract Background People with advanced human immunodeficiency virus (HIV) (CD4 &lt; 50) remain at high risk of tuberculosis (TB) or death despite the initiation of antiretroviral therapy (ART). We aimed to identify immunological profiles that were most predictive of incident TB disease and death. Methods The REMEMBER randomized clinical trial enrolled 850 participants with HIV (CD4 &lt; 50 cells/µL) at ART initiation to receive either empiric TB treatment or isoniazid preventive therapy (IPT). A case-cohort study (n = 257) stratified by country and treatment arm was performed. Cases were defined as incident TB or all-cause death within 48 weeks after ART initiation. Using multiplexed immunoassay panels and ELISA, 26 biomarkers were assessed in plasma. Results In total, 52 (6.1%) of 850 participants developed TB; 47 (5.5%) died (13 of whom had antecedent TB). Biomarkers associated with incident TB overlapped with those associated with death (interleukin [IL]-1β, IL-6). Biomarker levels declined over time in individuals with incident TB while remaining persistently elevated in those who died. Dividing the cohort into development and validation sets, the final model of 6 biomarkers (CXCL10, IL-1β, IL-10, sCD14, tumor necrosis factor [TNF]-α, and TNF-β) achieved a sensitivity of 0.90 (95% confidence interval [CI]: .87–.94) and a specificity of 0.71(95% CI: .68–.75) with an area under the curve (AUC) of 0.81 (95% CI: .78–.83) for incident TB. Conclusion Among people with advanced HIV, a parsimonious inflammatory biomarker signature predicted those at highest risk for developing TB despite initiation of ART and TB preventive therapies. The signature may be a promising stratification tool to select patients who may benefit from increased monitoring and novel interventions. Clinical Trials Registration NCT01380080


2005 ◽  
Vol 59 (2) ◽  
pp. 174-182 ◽  
Author(s):  
Bregt S. Kappelhoff ◽  
Alwin D. R. Huitema ◽  
Kristel M. L. Crommentuyn ◽  
Jan W. Mulder ◽  
Pieter L. Meenhorst ◽  
...  

PLoS ONE ◽  
2011 ◽  
Vol 6 (4) ◽  
pp. e18578 ◽  
Author(s):  
Thierry Buclin ◽  
Amalio Telenti ◽  
Rafael Perera ◽  
Chantal Csajka ◽  
Hansjakob Furrer ◽  
...  

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