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2.
Front Mol Biosci ; 10: 1144001, 2023.
Article in English | MEDLINE | ID: mdl-37842636

ABSTRACT

Introduction: Accurate and rapid diagnostics paired with effective tracking and tracing systems are key to halting the spread of infectious diseases, limiting the emergence of new variants and to monitor vaccine efficacy. The current gold standard test (RT-qPCR) for COVID-19 is highly accurate and sensitive, but is time-consuming, and requires expensive specialised, lab-based equipment. Methods: Herein, we report on the development of a SARS-CoV-2 (COVID-19) rapid and inexpensive diagnostic platform that relies on a reverse-transcription loop-mediated isothermal amplification (RT-LAMP) assay and a portable smart diagnostic device. Automated image acquisition and an Artificial Intelligence (AI) deep learning model embedded in the Virus Hunter 6 (VH6) device allow to remove any subjectivity in the interpretation of results. The VH6 device is also linked to a smartphone companion application that registers patients for swab collection and manages the entire process, thus ensuring tests are traced and data securely stored. Results: Our designed AI-implemented diagnostic platform recognises the nucleocapsid protein gene of SARS-CoV-2 with high analytical sensitivity and specificity. A total of 752 NHS patient samples, 367 confirmed positives for coronavirus disease (COVID-19) and 385 negatives, were used for the development and validation of the test and the AI-assisted platform. The smart diagnostic platform was then used to test 150 positive clinical samples covering a dynamic range of clinically meaningful viral loads and 250 negative samples. When compared to RT-qPCR, our AI-assisted diagnostics platform was shown to be reliable, highly specific (100%) and sensitive (98-100% depending on viral load) with a limit of detection of 1.4 copies of RNA per µL in 30 min. Using this data, our CE-IVD and MHRA approved test and associated diagnostic platform has been approved for medical use in the United Kingdom under the UK Health Security Agency's Medical Devices (Coronavirus Test Device Approvals, CTDA) Regulations 2022. Laboratory and in-silico data presented here also indicates that the VIDIIA diagnostic platform is able to detect the main variants of concern in the United Kingdom (September 2023). Discussion: This system could provide an efficient, time and cost-effective platform to diagnose SARS-CoV-2 and other infectious diseases in resource-limited settings.

3.
Environ Int ; 171: 107707, 2023 01.
Article in English | MEDLINE | ID: mdl-36566718

ABSTRACT

BACKGROUND: Human, animal, and environmental health are increasingly threatened by the emergence and spread of antibiotic resistance. Inappropriate use of antibiotic treatments commonly contributes to this threat, but it is also becoming apparent that multiple, interconnected environmental factors can play a significant role. Thus, a One Health approach is required for a comprehensive understanding of the environmental dimensions of antibiotic resistance and inform science-based decisions and actions. The broad and multidisciplinary nature of the problem poses several open questions drawing upon a wide heterogeneous range of studies. OBJECTIVE: This study seeks to collect and catalogue the evidence of the potential effects of environmental factors on the abundance or detection of antibiotic resistance determinants in the outdoor environment, i.e., antibiotic resistant bacteria and mobile genetic elements carrying antibiotic resistance genes, and the effect on those caused by local environmental conditions of either natural or anthropogenic origin. METHODS: Here, we describe the protocol for a systematic evidence map to address this, which will be performed in adherence to best practice guidelines. We will search the literature from 1990 to present, using the following electronic databases: MEDLINE, Embase, and the Web of Science Core Collection as well as the grey literature. We shall include full-text, scientific articles published in English. Reviewers will work in pairs to screen title, abstract and keywords first and then full-text documents. Data extraction will adhere to a code book purposely designed. Risk of bias assessment will not be conducted as part of this SEM. We will combine tables, graphs, and other suitable visualisation techniques to compile a database i) of studies investigating the factors associated with the prevalence of antibiotic resistance in the environment and ii) map the distribution, network, cross-disciplinarity, impact and trends in the literature.


Subject(s)
Anti-Bacterial Agents , Bacteria , Animals , Humans , Prevalence , Drug Resistance, Microbial/genetics , Bacteria/genetics , Bias , Anti-Bacterial Agents/pharmacology
4.
Article in English | MEDLINE | ID: mdl-35130168

ABSTRACT

Predicting Antimicrobial Resistance (AMR) from genomic data has important implications for human and animal healthcare, and especially given its potential for more rapid diagnostics and informed treatment choices. With the recent advances in sequencing technologies, applying machine learning techniques for AMR prediction have indicated promising results. Despite this, there are shortcomings in the literature concerning methodologies suitable for multi-drug AMR prediction and especially where samples with missing labels exist. To address this shortcoming, we introduce a Rectified Classifier Chain (RCC) method for predicting multi-drug resistance. This RCC method was tested using annotated features of genomics sequences and compared with similar multi-label classification methodologies. We found that applying the eXtreme Gradient Boosting (XGBoost) base model to our RCC model outperformed the second-best model, XGBoost based binary relevance model, by 3.3% in Hamming accuracy and 7.8% in F1-score. Additionally, we note that in the literature machine learning models applied to AMR prediction typically are unsuitable for identifying biomarkers informative of their decisions; in this study, we show that biomarkers contributing to AMR prediction can also be identified using the proposed RCC method. We expect this can facilitate genome annotation and pave the path towards identifying new biomarkers indicative of AMR.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Animals , Humans , Drug Resistance, Microbial , Genomics , Machine Learning
5.
Viruses ; 12(9)2020 09 01.
Article in English | MEDLINE | ID: mdl-32883050

ABSTRACT

Until vaccines and effective therapeutics become available, the practical solution to transit safely out of the current coronavirus disease 19 (CoVID-19) lockdown may include the implementation of an effective testing, tracing and tracking system. However, this requires a reliable and clinically validated diagnostic platform for the sensitive and specific identification of SARS-CoV-2. Here, we report on the development of a de novo, high-resolution and comparative genomics guided reverse-transcribed loop-mediated isothermal amplification (LAMP) assay. To further enhance the assay performance and to remove any subjectivity associated with operator interpretation of results, we engineered a novel hand-held smart diagnostic device. The robust diagnostic device was further furnished with automated image acquisition and processing algorithms and the collated data was processed through artificial intelligence (AI) pipelines to further reduce the assay run time and the subjectivity of the colorimetric LAMP detection. This advanced AI algorithm-implemented LAMP (ai-LAMP) assay, targeting the RNA-dependent RNA polymerase gene, showed high analytical sensitivity and specificity for SARS-CoV-2. A total of ~200 coronavirus disease (CoVID-19)-suspected NHS patient samples were tested using the platform and it was shown to be reliable, highly specific and significantly more sensitive than the current gold standard qRT-PCR. Therefore, this system could provide an efficient and cost-effective platform to detect SARS-CoV-2 in resource-limited laboratories.


Subject(s)
Artificial Intelligence , Betacoronavirus/isolation & purification , Coronavirus Infections/virology , Molecular Diagnostic Techniques/methods , Nucleic Acid Amplification Techniques/methods , Pneumonia, Viral/virology , Animals , COVID-19 , COVID-19 Testing , Chlorocebus aethiops , Clinical Laboratory Techniques/methods , Coronavirus Infections/diagnosis , Dogs , Humans , Madin Darby Canine Kidney Cells , Pandemics , Pneumonia, Viral/diagnosis , RNA, Viral/genetics , Real-Time Polymerase Chain Reaction , SARS-CoV-2 , Sensitivity and Specificity , Vero Cells
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