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1.
Bioinformatics ; 37(7): 1024-1025, 2021 05 17.
Artículo en Inglés | MEDLINE | ID: mdl-32777813

RESUMEN

SUMMARY: Polymerase chain reaction-based assays are the current gold standard for detecting and diagnosing SARS-CoV-2. However, as SARS-CoV-2 mutates, we need to constantly assess whether existing PCR-based assays will continue to detect all known viral strains. To enable the continuous monitoring of SARS-CoV-2 assays, we have developed a web-based assay validation algorithm that checks existing PCR-based assays against the ever-expanding genome databases for SARS-CoV-2 using both thermodynamic and edit-distance metrics. The assay-screening results are displayed as a heatmap, showing the number of mismatches between each detection and each SARS-CoV-2 genome sequence. Using a mismatch threshold to define detection failure, assay performance is summarized with the true-positive rate (recall) to simplify assay comparisons. AVAILABILITY AND IMPLEMENTATION: The assay evaluation website and supporting software are Open Source and freely available at https://covid19.edgebioinformatics.org/#/assayValidation, https://github.com/jgans/thermonucleotide BLAST and https://github.com/LANL-Bioinformatics/assay_validation. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Asunto(s)
COVID-19 , SARS-CoV-2 , Prueba de COVID-19 , Humanos , Reacción en Cadena de la Polimerasa , Sensibilidad y Especificidad
2.
PLOS Glob Public Health ; 2(2): e0000207, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36962401

RESUMEN

Viral pathogens can rapidly evolve, adapt to novel hosts, and evade human immunity. The early detection of emerging viral pathogens through biosurveillance coupled with rapid and accurate diagnostics are required to mitigate global pandemics. However, RNA viruses can mutate rapidly, hampering biosurveillance and diagnostic efforts. Here, we present a novel computational approach called FEVER (Fast Evaluation of Viral Emerging Risks) to design assays that simultaneously accomplish: 1) broad-coverage biosurveillance of an entire group of viruses, 2) accurate diagnosis of an outbreak strain, and 3) mutation typing to detect variants of public health importance. We demonstrate the application of FEVER to generate assays to simultaneously 1) detect sarbecoviruses for biosurveillance; 2) diagnose infections specifically caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); and 3) perform rapid mutation typing of the D614G SARS-CoV-2 spike variant associated with increased pathogen transmissibility. These FEVER assays had a high in silico recall (predicted positive) up to 99.7% of 525,708 SARS-CoV-2 sequences analyzed and displayed sensitivities and specificities as high as 92.4% and 100% respectively when validated in 100 clinical samples. The D614G SARS-CoV-2 spike mutation PCR test was able to identify the single nucleotide identity at position 23,403 in the viral genome of 96.6% SARS-CoV-2 positive samples without the need for sequencing. This study demonstrates the utility of FEVER to design assays for biosurveillance, diagnostics, and mutation typing to rapidly detect, track, and mitigate future outbreaks and pandemics caused by emerging viruses.

3.
Biosensors (Basel) ; 11(10)2021 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-34677323

RESUMEN

Detection methods that do not require nucleic acid amplification are advantageous for viral diagnostics due to their rapid results. These platforms could provide information for both accurate diagnoses and pandemic surveillance. Influenza virus is prone to pandemic-inducing genetic mutations, so there is a need to apply these detection platforms to influenza diagnostics. Here, we analyzed the Fast Evaluation of Viral Emerging Risks (FEVER) pipeline on ultrasensitive detection platforms, including a waveguide-based optical biosensor and a flow cytometry bead-based assay. The pipeline was also evaluated in silico for sequence coverage in comparison to the U.S. Centers for Disease Control and Prevention's (CDC) influenza A and B diagnostic assays. The influenza FEVER probe design had a higher tolerance for mismatched bases than the CDC's probes, and the FEVER probes altogether had a higher detection rate for influenza isolate sequences from GenBank. When formatted for use as molecular beacons, the FEVER probes detected influenza RNA as low as 50 nM on the waveguide-based optical biosensor and 1 nM on the flow cytometer. In addition to molecular beacons, which have an inherently high background signal we also developed an exonuclease selection method that could detect 500 pM of RNA. The combination of high-coverage probes developed using the FEVER pipeline coupled with ultrasensitive optical biosensors is a promising approach for future influenza diagnostic and biosurveillance applications.


Asunto(s)
Gripe Humana , Técnicas de Amplificación de Ácido Nucleico , Técnicas Biosensibles , Humanos , Orthomyxoviridae , ARN , Sensibilidad y Especificidad
4.
Epilepsia ; 51(10): 2038-46, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20384719

RESUMEN

PURPOSE: To characterize prospective neurodevelopmental changes in brain structure in children with new and recent-onset epilepsy compared to healthy controls. METHODS: Thirty-four healthy controls (mean age 12.9 years) and 38 children with new/recent-onset idiopathic epilepsy (mean age 12.9 years) underwent 1.5 T magnetic resonance imaging (MRI) at baseline and 2 years later. Prospective changes in total cerebral and lobar gray and white matter volumes were compared within and between groups. RESULTS: Prospective changes in gray matter volume were comparable for the epilepsy and control groups, with significant (p < 0.0001) reduction in total cerebral gray matter, due primarily to significant (p < 0.001) reductions in frontal and parietal gray matter. Prospective white matter volume changes differed between groups. Controls exhibited a significant (p = 0.0012) increase in total cerebral white matter volume due to significant (p < 0.001) volume increases in the frontal, parietal, and temporal lobes. In contrast, the epilepsy group exhibited nonsignificant white matter volume change in the total cerebrum (p = 0.51) as well as across all lobes (all p's > 0.06). The group by white matter volume change interactions were significant for total cerebrum (p = 0.04) and frontal lobe (p = 0.04). DISCUSSION: Children with new and recent-onset epilepsy exhibit an altered pattern of brain development characterized by delayed age-appropriate increase in white matter volume. These findings may affect cognitive development through reduced brain connectivity and may also be related to the impairments in executive function commonly reported in this population.


Asunto(s)
Encéfalo/patología , Epilepsia/patología , Adolescente , Edad de Inicio , Atrofia/patología , Encéfalo/crecimiento & desarrollo , Corteza Cerebral/crecimiento & desarrollo , Corteza Cerebral/patología , Niño , Estudios de Cohortes , Epilepsia/diagnóstico , Femenino , Lóbulo Frontal/crecimiento & desarrollo , Lóbulo Frontal/patología , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética/estadística & datos numéricos , Masculino , Lóbulo Parietal/crecimiento & desarrollo , Lóbulo Parietal/patología , Estudios Prospectivos
5.
Schizophr Res ; 66(1): 31-9, 2004 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-14693350

RESUMEN

BACKGROUND: Proton magnetic resonance spectroscopy (1H-MRS) studies of schizophrenia suggest an effect of the disease or of antipsychotic medications on brain N-acetyl aspartate (NAA), a marker of neuronal viability. We studied in the rat the effect of antipsychotic drugs on NAA in several brain regions where NAA reductions have been reported in chronically medicated patients with schizophrenia. METHODS: Three groups of nine rats each were treated with haloperidol (6 mg/kg/day), clozapine (70 mg/kg/day) and vehicle for 6 weeks and were sacrificed. Concentrations of NAA were determined by high-performance liquid chromatography (HPLC) from the following brain regions: cortex, striatum, thalamus, hippocampus and cerebellum. RESULTS: Mixed-factorial ANOVA of NAA concentrations revealed no significant effect of drug group [F(2, 24) = 0.034; p = 0.966] or a group by brain region interaction [F(8, 44) = 0.841; p = 0.572]. There was a significant main effect of region [F(4, 21) = 6.104; p = 0.002] with higher NAA in the cortex. CONCLUSIONS: These results are consistent with the only other study of the effect of typical and atypical antipsychotic drugs on NAA in the rat brain. The well-documented lower NAA in chronically treated schizophrenia patients is probably not a simple effect of antipsychotic medications.


Asunto(s)
Antipsicóticos/farmacología , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Encéfalo/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Clozapina/farmacología , Haloperidol/farmacología , Animales , Mapeo Encefálico , Cromatografía Líquida de Alta Presión , Espectroscopía de Resonancia Magnética , Masculino , Neuronas/efectos de los fármacos , Ratas , Ratas Sprague-Dawley
6.
Epilepsy Res ; 88(2-3): 208-14, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20044239

RESUMEN

The purpose of this investigation was to examine the diffusion properties of cerebral white matter in children with recent onset epilepsy (n=19) compared to healthy controls (n=11). Subjects underwent DTI with quantification of mean diffusion (MD), fractional anisotropy (FA), axial diffusivity (D(ax)) and radial diffusivity (D(rad)) for regions of interest including anterior and posterior corpus callosum, fornix, cingulum, and internal and external capsules. Quantitative volumetrics were also performed for the corpus callosum and its subregions (anterior, midbody and posterior) and total lobar white and gray matter for the frontal, parietal, temporal and occipital lobes. The results demonstrated no group differences in total lobar gray or white matter volumes or volume of the corpus callosum and its subregions, but did show reduced FA and increased D(rad) in the posterior corpus callosum and cingulum. These results provide the earliest indication of microstructural abnormality in cerebral white matter among children with idiopathic epilepsies. This abnormality occurs in the context of normal volumetrics and suggests disruption in myelination processes.


Asunto(s)
Epilepsia/fisiopatología , Telencéfalo/fisiopatología , Adolescente , Anisotropía , Mapeo Encefálico , Niño , Imagen de Difusión Tensora , Electroencefalografía , Epilepsia/patología , Humanos , Procesamiento de Imagen Asistido por Computador , Fibras Nerviosas Mielínicas/patología , Fibras Nerviosas Mielínicas/fisiología , Tamaño de los Órganos , Telencéfalo/patología
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