Deep Domain Adaptation Enhances Amplification Curve Analysis for Single-Channel Multiplexing in Real-Time PCR.



Mao, Ye, Xu, Ke, Miglietta, Luca, Kreitmann, Louis, Moser, Nicolas, Georgiou, Pantelis, Holmes, Alison ORCID: 0000-0001-5554-5743 and Rodriguez-Manzano, Jesus
(2023) Deep Domain Adaptation Enhances Amplification Curve Analysis for Single-Channel Multiplexing in Real-Time PCR. IEEE journal of biomedical and health informatics, 27 (6). pp. 3093-3103.

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Abstract

Data-driven approaches for molecular diagnostics are emerging as an alternative to perform an accurate and inexpensive multi-pathogen detection. A novel technique called Amplification Curve Analysis (ACA) has been recently developed by coupling machine learning and real-time Polymerase Chain Reaction (qPCR) to enable the simultaneous detection of multiple targets in a single reaction well. However, target classification purely relying on the amplification curve shapes faces several challenges, such as distribution discrepancies between different data sources (i.e., training vs testing). Optimisation of computational models is required to achieve higher performance of ACA classification in multiplex qPCR through the reduction of those discrepancies. Here, we proposed a novel transformer-based conditional domain adversarial network (T-CDAN) to eliminate data distribution differences between the source domain (synthetic DNA data) and the target domain (clinical isolate data). The labelled training data from the source domain and unlabelled testing data from the target domain are fed into the T-CDAN, which learns both domains' information simultaneously. After mapping the inputs into a domain-irrelevant space, T-CDAN removes the feature distribution differences and provides a clearer decision boundary for the classifier, resulting in a more accurate pathogen identification. Evaluation of 198 clinical isolates containing three types of carbapenem-resistant genes (bla<sub>NDM</sub>, bla<sub>IMP</sub> and bla<sub>OXA-48</sub>) illustrates a curve-level accuracy of 93.1% and a sample-level accuracy of 97.0% using T-CDAN, showing an accuracy improvement of 20.9% and 4.9% respectively. This research emphasises the importance of deep domain adaptation to enable high-level multiplexing in a single qPCR reaction, providing a solid approach to extend qPCR instruments' capabilities in real-world clinical applications.

Item Type: Article
Uncontrolled Keywords: Nucleic Acid Amplification Techniques, Computer Simulation, Real-Time Polymerase Chain Reaction, Machine Learning
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 29 Sep 2023 09:14
Last Modified: 18 Nov 2023 02:07
DOI: 10.1109/jbhi.2023.3257727
Open Access URL: https://doi.org/10.1109/JBHI.2023.3257727
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3173191