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Please use this identifier to cite or link to this item: 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
Citation: 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.
URI: http://hdl.handle.net/1942/24254
DOI: 10.1371/journal.pone.0177384
ISI #: 000402062800016
ISSN: 1932-6203
Category: A1
Type: Journal Contribution
Appears in Collections: Research publications

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