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.

An artificial intelligence-assisted low-cost portable device for the rapid detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is presented here. This standalone temperature-controlled device houses tubes designed for conducting reverse transcription loop-mediated isothermal amplification (RT-LAMP) assays. Moreover, the device utilises tubes illuminated by LEDs, an in-built camera, and a small onboard computer with automated image acquisition and processing algorithms. This intelligent device significantly reduces the normal assay run time and removes the subjectivity associated with operator interpretation of colourimetric RT-LAMP results. To further improve this device’s usability, a mobile app has been integrated into the system to control the LAMP assay environment and to visually display the assay results by connecting the device to a smartphone via Bluetooth. This study was undertaken using ~5000 images produced from the ~200 LAMP amplification assays using the prototype device. Synthetic RNA and a small panel of positive and negative SARS-CoV-2 patient samples were assayed for this study. State-of-the-art image processing and artificial intelligence algorithms were applied to these images to analyse them and to select the most efficient algorithm. The template matching algorithm for image extraction and MobileNet CNN architecture for classification results provided 98.0% accuracy with an average run time of 20 min to confirm the endpoint result. Two working points were chosen based on the best compromise between sensitivity and specificity. The high sensitivity point has a sensitivity value of 99.12% and specificity value of 70.8%, while at the high specificity point, the sensitivity is 96.05% and specificity 93.59%. Furthermore, this device provides an efficient and cost-effective platform for non-health professionals to detect not only SARS-CoV-2 but also other pathogens in resource-limited laboratories, factories, airports, schools, universities, and homes.

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.

Until vaccines and effective therapeutics become available, the practical way to transit safely out of the current 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 result, 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 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. The system could provide an efficient and cost-effective platform to detect SARS-CoV-2 in resource-limited laboratories.

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