Bridging the gaps in test interpretation of SARS-CoV-2 through Bayesian network modelling.
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ABSTRACT:
SUBMITTER: Wu Y
PROVIDER: S-EPMC8314199 | biostudies-literature | 2021 Jun
REPOSITORIES: biostudies-literature
Publications
Bridging the gaps in test interpretation of SARS-CoV-2 through Bayesian network modelling.
Wu Yue Y Foley David D Ramsay Jessica J Woodberry Owen O Mascaro Steven S Nicholson Ann E AE Snelling Tom T
Epidemiology and infection 20210623
Similar Datasets
Project description:In the early phases of growth, resurgent epidemic waves of SARS-CoV-2 incidence have been characterised by localised outbreaks. Therefore, understanding the geographic dispersion of emerging variants at the start of an outbreak is key for situational public health awareness. Using telecoms data, we derived mobility networks describing the movement patterns between local authorities in England, which we have used to inform the spatial structure of a Bayesian BYM2 model. Surge testing interventions can result in spatio-temporal sampling bias, and we account for this by extending the BYM2 model to include a random effect for each timepoint in a given area. Simulated-scenario modelling and real-world analyses of each variant that became dominant in England were conducted using our BYM2 model at local authority level in England. Simulated datasets were created using a stochastic metapopulation model, with the transmission rates between different areas parameterised using telecoms mobility data. Different scenarios were constructed to reproduce real-world spatial dispersion patterns that could prove challenging to inference, and we used these scenarios to understand the performance characteristics of the BYM2 model. The model performed better than unadjusted test positivity in all the simulation-scenarios, and in particular when sample sizes were small, or data was missing for geographical areas. Through the analyses of emerging variant transmission across England, we found a reduction in the early growth phase geographic clustering of later dominant variants as England became more interconnected from early 2022 and public health interventions were reduced. We have also shown the recent increased geographic spread and dominance of variants with similar mutations in the receptor binding domain, which may be indicative of convergent evolution of SARS-CoV-2 variants.
| S-EPMC10756685 | biostudies-literature
Project description:ObjectiveTo use natural language processing (NLP) of clinical notes to augment existing structured electronic health record (EHR) data for classification of a patient's menopausal status.Materials and methodsA rule-based NLP system was designed to capture evidence of a patient's menopause status including dates of a patient's last menstrual period, reproductive surgeries, and postmenopause diagnosis as well as their use of birth control and menstrual interruptions. NLP-derived output was used in combination with structured EHR data to classify a patient's menopausal status. NLP processing and patient classification were performed on a cohort of 307 512 female Veterans receiving healthcare at the US Department of Veterans Affairs (VA).ResultsNLP was validated at 99.6% precision. Including the NLP-derived data into a menopause phenotype increased the number of patients with data relevant to their menopausal status by 118%. Using structured codes alone, 81 173 (27.0%) are able to be classified as postmenopausal or premenopausal. However, with the inclusion of NLP, this number increased 167 804 (54.6%) patients. The premenopausal category grew by 532.7% with the inclusion of NLP data.DiscussionBy employing NLP, it became possible to identify documented data elements that predate VA care, originate outside VA networks, or have no corresponding structured field in the VA EHR that would be otherwise inaccessible for further analysis.ConclusionNLP can be used to identify concepts relevant to a patient's menopausal status in clinical notes. Adding NLP-derived data to an algorithm classifying a patient's menopausal status significantly increases the number of patients classified using EHR data, ultimately enabling more detailed assessments of the impact of menopause on health outcomes.
| S-EPMC10901606 | biostudies-literature
Project description:As countries decide on vaccination strategies and how to ease movement restrictions, estimating the proportion of the population previously infected with SARS-CoV-2 is important for predicting the future burden of COVID-19. This proportion is usually estimated from serosurvey data in two steps: first the proportion above a threshold antibody level is calculated, then the crude estimate is adjusted using external estimates of sensitivity and specificity. A drawback of this approach is that the PCR-confirmed cases used to estimate the sensitivity of the threshold may not be representative of cases in the wider population-e.g., they may be more recently infected and more severely symptomatic. Mixture modelling offers an alternative approach that does not require external data from PCR-confirmed cases. Here we illustrate the bias in the standard threshold-based approach by comparing both approaches using data from several Kenyan serosurveys. We show that the mixture model analysis produces estimates of previous infection that are often substantially higher than the standard threshold analysis.
| S-EPMC8548402 | biostudies-literature
Project description:The sudden loss of smell is among the earliest and most prevalent symptoms of COVID-19 when measured with a clinical psychophysical test. Research has shown the potential impact of frequent screening for olfactory dysfunction, but existing tests are expensive and time consuming. We developed a low-cost ($0.50/test) rapid psychophysical olfactory test (KOR) for frequent testing and a model-based COVID-19 screening framework using a Bayes Network symptoms model. We trained and validated the model on two samples: suspected COVID-19 cases in five healthcare centers (n = 926; 33% prevalence, 309 RT-PCR confirmed) and healthy miners (n = 1,365; 1.1% prevalence, 15 RT-PCR confirmed). The model predicted COVID-19 status with 76% and 96% accuracy in the healthcare and miners samples, respectively (healthcare: AUC = 0.79 [0.75-0.82], sensitivity: 59%, specificity: 87%; miners: AUC = 0.71 [0.63-0.79], sensitivity: 40%, specificity: 97%, at 0.50 infection probability threshold). Our results highlight the potential for low-cost, frequent, accessible, routine COVID-19 testing to support society's reopening.
| S-EPMC8580551 | biostudies-literature
Project description:Although seasonal variation has a known influence on the transmission of several respiratory viral infections, its role in SARS-CoV-2 transmission remains unclear. While there is a sizable and growing literature on environmental drivers of COVID-19 transmission, recent reviews have highlighted conflicting and inconclusive findings. This indeterminacy partly owes to the fact that seasonal variation relates to viral transmission by a complicated web of causal pathways, including many interacting biological and behavioural factors. Since analyses of specific factors cannot determine the aggregate strength of seasonal forcing, we sidestep the challenge of disentangling various possible causal paths in favor of a holistic approach. We model seasonality as a sinusoidal variation in transmission and infer a single Bayesian estimate of the overall seasonal effect. By extending two state-of-the-art models of non-pharmaceutical intervention (NPI) effects and their datasets covering 143 regions in temperate Europe, we are able to adjust our estimates for the role of both NPIs and mobility patterns in reducing transmission. We find strong seasonal patterns, consistent with a reduction in the time-varying reproduction number R(t) (the expected number of new infections generated by an infectious individual at time t) of 42.1% (95% CI: 24.7%-53.4%) from the peak of winter to the peak of summer. These results imply that the seasonality of SARS-CoV-2 transmission is comparable in magnitude to the most effective individual NPIs but less than the combined effect of multiple interventions.
| S-EPMC9455844 | biostudies-literature
Project description: Not available
| S-BSST379 | biostudies-other
Project description:BackgroundWhen tackling complex public health challenges such as childhood obesity, interventions focused on immediate causes, such as poor diet and physical inactivity, have had limited success, largely because upstream root causes remain unresolved. A priority is to develop new modelling frameworks to infer the causal structure of complex chronic disease networks, allowing disease "on-ramps" to be identified and targeted.MethodsThe system surrounding childhood obesity was modelled as a Bayesian network, using data from The Longitudinal Study of Australian Children. The existence and directions of the dependencies between factors represent possible causal pathways for childhood obesity and were encoded in directed acyclic graphs (DAGs). The posterior distribution of the DAGs was estimated using the Partition Markov chain Monte Carlo.ResultsWe have implemented structure learning for each dataset at a single time point. For each wave and cohort, socio-economic status was central to the DAGs, implying that socio-economic status drives the system regarding childhood obesity. Furthermore, the causal pathway socio-economic status and/or parental high school levels → parental body mass index (BMI) → child's BMI existed in over 99.99% of posterior DAG samples across all waves and cohorts. For children under the age of 8 years, the most influential proximate causal factors explaining child BMI were birth weight and parents' BMI. After age 8 years, free time activity became an important driver of obesity, while the upstream factors influencing free time activity for boys compared with girls were different.ConclusionsChildhood obesity is largely a function of socio-economic status, which is manifest through numerous downstream factors. Parental high school levels entangle with socio-economic status, and hence, are on-ramp to childhood obesity. The strong and independent causal relationship between birth weight and childhood BMI suggests a biological link. Our study implies that interventions that improve the socio-economic status, including through increasing high school completion rates, may be effective in reducing childhood obesity prevalence.
| S-EPMC10031893 | biostudies-literature
Project description:Diagnostic tests that detect antibodies (AB) against SARS-CoV-2 for evaluation of seroprevalence and guidance of health care measures are important tools for managing the COVID-19 pandemic. Current tests have certain limitations with regard to turnaround time, costs and availability, particularly in point-of-care (POC) settings. We established a hemagglutination-based AB test that is based on bi-specific proteins which contain a dromedary-derived antibody (nanobody) binding red blood cells (RBD) and a SARS-CoV-2-derived antigen, such as the receptor-binding domain of the Spike protein (Spike-RBD). While the nanobody mediates swift binding to RBC, the antigen moiety directs instantaneous, visually apparent hemagglutination in the presence of SARS-CoV-2-specific AB generated in COVID-19 patients or vaccinated individuals. Method comparison studies with assays cleared by emergency use authorization demonstrate high specificity and sensitivity. To further increase objectivity of test interpretation, we developed an image analysis tool based on digital image acquisition (via a cell phone) and a machine learning algorithm based on defined sample-training and -validation datasets. Preliminary data, including a small clinical study, provides proof of principle for test performance in a POC setting. Together, the data support the interpretation that this AB test format, which we refer to as 'NanoSpot.ai', is suitable for POC testing, can be manufactured at very low costs and, based on its generic mode of action, can likely be adapted to a variety of other pathogens.
| S-EPMC8718524 | biostudies-literature
Project description:Genus Aspergillus represents a widely spread genus of fungi that is highly popular for possessing potent medicinal potential comprising mainly antimicrobial, cytotoxic and antioxidant properties. They are highly attributed to its richness by alkaloids, terpenes, steroids and polyketons. This review aimed to comprehensively explore the diverse alkaloids isolated and identified from different species of genus Aspergillus that were found to be associated with different marine organisms regarding their chemistry and biology. Around 174 alkaloid metabolites were reported, 66 of which showed important biological activities with respect to the tested biological activities mainly comprising antiviral, antibacterial, antifungal, cytotoxic, antioxidant and antifouling activities. Besides, in silico studies on different microbial proteins comprising DNA-gyrase, topoisomerase IV, dihydrofolate reductase, transcriptional regulator TcaR (protein), and aminoglycoside nucleotidyl transferase were done for sixteen alkaloids that showed anti-infective potential for better mechanistic interpretation of their probable mode of action. The inhibitory potential of compounds vs. Angiotensin-Converting Enzyme 2 (ACE2) as an important therapeutic target combating COVID-19 infection and its complication was also examined using molecular docking. Fumigatoside E showed the best fitting within the active sites of all the examined proteins. Thus, Aspergillus species isolated from marine organisms could afford bioactive entities combating infectious diseases.
| S-EPMC7918500 | biostudies-literature
Project description:Since its introduction in the human population, SARS-CoV-2 has evolved into multiple clades, but the events in its intrahost diversification are not well understood. Here, we compare three-dimensional (3D) self-organized neural haplotype maps (SOMs) of SARS-CoV-2 from thirty individual nasopharyngeal diagnostic samples obtained within a 19-day interval in Madrid (Spain), at the time of transition between clades 19 and 20. SOMs have been trained with the haplotype repertoire present in the mutant spectra of the nsp12- and spike (S)-coding regions. Each SOM consisted of a dominant neuron (displaying the maximum frequency), surrounded by a low-frequency neuron cloud. The sequence of the master (dominant) neuron was either identical to that of the reference Wuhan-Hu-1 genome or differed from it at one nucleotide position. Six different deviant haplotype sequences were identified among the master neurons. Some of the substitutions in the neural clouds affected critical sites of the nsp12-nsp8-nsp7 polymerase complex and resulted in altered kinetics of RNA synthesis in an in vitro primer extension assay. Thus, the analysis has identified mutations that are relevant to modification of viral RNA synthesis, present in the mutant clouds of SARS-CoV-2 quasispecies. These mutations most likely occurred during intrahost diversification in several COVID-19 patients, during an initial stage of the pandemic, and within a brief time period.
| S-EPMC10927536 | biostudies-literature