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Computational design of probes to detect bacterial genomes by multivalent binding
Rapid methods for diagnosis of bacterial infections are urgently needed to reduce inappropriate use of antibiotics, which contributes to antimicrobial resistance. In many rapid diagnostic methods, DNA oligonucleotide probes, attached to a surface, bind to specific nucleotide sequences in the DNA of...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183166/ https://www.ncbi.nlm.nih.gov/pubmed/32241887 http://dx.doi.org/10.1073/pnas.1918274117 |
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author | Curk, Tine Brackley, Chris A. Farrell, James D. Xing, Zhongyang Joshi, Darshana Direito, Susana Bren, Urban Angioletti-Uberti, Stefano Dobnikar, Jure Eiser, Erika Frenkel, Daan Allen, Rosalind J. |
author_facet | Curk, Tine Brackley, Chris A. Farrell, James D. Xing, Zhongyang Joshi, Darshana Direito, Susana Bren, Urban Angioletti-Uberti, Stefano Dobnikar, Jure Eiser, Erika Frenkel, Daan Allen, Rosalind J. |
author_sort | Curk, Tine |
collection | PubMed |
description | Rapid methods for diagnosis of bacterial infections are urgently needed to reduce inappropriate use of antibiotics, which contributes to antimicrobial resistance. In many rapid diagnostic methods, DNA oligonucleotide probes, attached to a surface, bind to specific nucleotide sequences in the DNA of a target pathogen. Typically, each probe binds to a single target sequence; i.e., target–probe binding is monovalent. Here we show using computer simulations that the detection sensitivity and specificity can be improved by designing probes that bind multivalently to the entire length of the pathogen genomic DNA, such that a given probe binds to multiple sites along the target DNA. Our results suggest that multivalent targeting of long pieces of genomic DNA can allow highly sensitive and selective binding of the target DNA, even if competing DNA in the sample also contains binding sites for the same probe sequences. Our results are robust to mild fragmentation of the bacterial genome. Our conclusions may also be relevant for DNA detection in other fields, such as disease diagnostics more broadly, environmental management, and food safety. |
format | Online Article Text |
id | pubmed-7183166 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-71831662020-04-29 Computational design of probes to detect bacterial genomes by multivalent binding Curk, Tine Brackley, Chris A. Farrell, James D. Xing, Zhongyang Joshi, Darshana Direito, Susana Bren, Urban Angioletti-Uberti, Stefano Dobnikar, Jure Eiser, Erika Frenkel, Daan Allen, Rosalind J. Proc Natl Acad Sci U S A Physical Sciences Rapid methods for diagnosis of bacterial infections are urgently needed to reduce inappropriate use of antibiotics, which contributes to antimicrobial resistance. In many rapid diagnostic methods, DNA oligonucleotide probes, attached to a surface, bind to specific nucleotide sequences in the DNA of a target pathogen. Typically, each probe binds to a single target sequence; i.e., target–probe binding is monovalent. Here we show using computer simulations that the detection sensitivity and specificity can be improved by designing probes that bind multivalently to the entire length of the pathogen genomic DNA, such that a given probe binds to multiple sites along the target DNA. Our results suggest that multivalent targeting of long pieces of genomic DNA can allow highly sensitive and selective binding of the target DNA, even if competing DNA in the sample also contains binding sites for the same probe sequences. Our results are robust to mild fragmentation of the bacterial genome. Our conclusions may also be relevant for DNA detection in other fields, such as disease diagnostics more broadly, environmental management, and food safety. National Academy of Sciences 2020-04-21 2020-04-02 /pmc/articles/PMC7183166/ /pubmed/32241887 http://dx.doi.org/10.1073/pnas.1918274117 Text en Copyright © 2020 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Physical Sciences Curk, Tine Brackley, Chris A. Farrell, James D. Xing, Zhongyang Joshi, Darshana Direito, Susana Bren, Urban Angioletti-Uberti, Stefano Dobnikar, Jure Eiser, Erika Frenkel, Daan Allen, Rosalind J. Computational design of probes to detect bacterial genomes by multivalent binding |
title | Computational design of probes to detect bacterial genomes by multivalent binding |
title_full | Computational design of probes to detect bacterial genomes by multivalent binding |
title_fullStr | Computational design of probes to detect bacterial genomes by multivalent binding |
title_full_unstemmed | Computational design of probes to detect bacterial genomes by multivalent binding |
title_short | Computational design of probes to detect bacterial genomes by multivalent binding |
title_sort | computational design of probes to detect bacterial genomes by multivalent binding |
topic | Physical Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183166/ https://www.ncbi.nlm.nih.gov/pubmed/32241887 http://dx.doi.org/10.1073/pnas.1918274117 |
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