Programmable design of isothermal nucleic acid diagnostic assays through abstraction-based models

Xu, G., Reboud, J. , Guo, Y., Yang, H., Gu, H., Fan, C., Qian, X. and Cooper, J. M. (2022) Programmable design of isothermal nucleic acid diagnostic assays through abstraction-based models. Nature Communications, 13, 1635. (doi: 10.1038/s41467-022-29101-1)

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Accelerating the design of nucleic acid amplification methods remains a critical challenge in the development of molecular tools to identify biomarkers to diagnose both infectious and non-communicable diseases. Many of the principles that underpin these mechanisms are often complex and can require iterative optimisation. Here we focus on creating a generalisable isothermal nucleic acid amplification methodology, describing the systematic implementation of abstraction-based models for the algorithmic design and application of assays. We demonstrate the simplicity, ease and flexibility of our approach using a software tool that provides amplification schemes de novo, based upon a user-input target sequence. The abstraction of reaction network predicts multiple reaction pathways across different strategies, facilitating assay optimisation for specific applications, including the ready design of multiplexed tests for short nucleic acid sequence miRNAs or for difficult pathogenic targets, such as highly mutating viruses.

Item Type:Articles
Additional Information:This work was supported by the Innovation Research Plan from the Shanghai Municipal Education Commission [ZXWF082101/056, GX], the Natural Science Foundation of Shanghai through the National Key Scientific Instrument and Equipment Development Project [NSFC 31927803, HG; NSFC 21991134, CF and T2188102, CF] and Exploratory Project [19ZR1476000, GX], the Engineering and Physical Sciences Research Council [EP/K027611/1, JC], and the European Research Council Advanced Investigator Award [340117 Biophononics, JC]. Funding for open access charge: EPSRC, JC.
Glasgow Author(s) Enlighten ID:Cooper, Professor Jonathan and Reboud, Dr Julien and Xu, Mr Gaolian
Authors: Xu, G., Reboud, J., Guo, Y., Yang, H., Gu, H., Fan, C., Qian, X., and Cooper, J. M.
College/School:College of Science and Engineering > School of Engineering > Biomedical Engineering
Journal Name:Nature Communications
Publisher:Nature Research
ISSN (Online):2041-1723
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in Nature Communications 13: 1635
Publisher Policy:Reproduced under a Creative Commons License
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Data DOI:10.5525/gla.researchdata.1100

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
168637Advanced Diagnostics using PhononicsJonathan CooperEngineering and Physical Sciences Research Council (EPSRC)EP/K027611/1ENG - Biomedical Engineering
169832Bio-PHONONICS: Advanced Microfluidics & Diagnostics using Acoustic Holograms – Bio-PhononicsJonathan CooperEuropean Research Council (ERC)340117ENG - Biomedical Engineering