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http://hdl.handle.net/1942/24254
Title: | Thermodynamic framework to assess low abundance DNA mutation detection by hybridization | Authors: | Willems, Hanny Jacobs, An Hadiwikarta, Wahyu Wijaya Venken, Tom VALKENBORG, Dirk Van Roy, Nadine Vandesompele, Jo HOOYBERGHS, Jef |
Issue Date: | 2017 | Publisher: | PUBLIC LIBRARY SCIENCE | Source: | PLOS ONE, 12(5), p. 1-18 (Art N° e0177384) | Abstract: | The knowledge of genomic DNA variations in patient samples has a high and increasing value for human diagnostics in its broadest sense. Although many methods and sensors to detect or quantify these variations are available or under development, the number of underlying physico-chemical detection principles is limited. One of these principles is the hybridization of sample target DNA versus nucleic acid probes. We introduce a novel thermodynamics approach and develop a framework to exploit the specific detection capabilities of nucleic acid hybridization, using generic principles applicable to any platform. As a case study, we detect point mutations in the KRAS oncogene on a microarray platform. For the given platform and hybridization conditions, we demonstrate the multiplex detection capability of hybridization and assess the detection limit using thermodynamic considerations; DNA containing point mutations in a background of wild type sequences can be identified down to at least 1% relative concentration. In order to show the clinical relevance, the detection capabilities are confirmed on challenging formalin-fixed paraffin-embedded clinical tumor samples. This enzyme-free detection framework contains the accuracy and efficiency to screen for hundreds of mutations in a single run with many potential applications in molecular diagnostics and the field of personalised medicine. | Notes: | [Willems, Hanny; Jacobs, An; Hadiwikarta, Wahyu Wijaya; Venken, Tom; Valkenborg, Dirk; Hooyberghs, Jef] VITO, Flemish Inst Technol Res, Mol, Belgium. [Hadiwikarta, Wahyu Wijaya] KULeuven, Inst Theoret Phys, Leuven, Belgium. [Valkenborg, Dirk] Hasselt Univ, Interuniv Inst Biostat & Stat Bioinformat, Diepenbeek, Belgium. [Van Roy, Nadine; Vandesompele, Jo] Univ Ghent, CMGG, Ghent, Belgium. [Vandesompele, Jo] Univ Ghent, CRIG, Ghent, Belgium. [Hooyberghs, Jef] Hasselt Univ, Theoret Phys, Diepenbeek, Belgium. | Document URI: | http://hdl.handle.net/1942/24254 | ISSN: | 1932-6203 | e-ISSN: | 1932-6203 | DOI: | 10.1371/journal.pone.0177384 | ISI #: | 000402062800016 | Rights: | t: © 2017 Willems et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2018 |
Appears in Collections: | Research publications |
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willems 1.pdf | Published version | 4.69 MB | Adobe PDF | View/Open |
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