Novel Algorithms for Improved Sensitivity in Non-Invasive Prenatal Testing

Abstract Non-invasive prenatal testing (NIPT) of cell-free DNA in maternal plasma, which is a mixture of maternal DNA and a low percentage of fetal DNA, can detect fetal aneuploidies using massively parallel sequencing. Because of the low percentage of fetal DNA, methods with high sensitivity and pr...

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Autores principales:	L. F. Johansson, E. N. de Boer, H. A. de Weerd, F. van Dijk, M. G. Elferink, G. H. Schuring-Blom, R. F. Suijkerbuijk, R. J. Sinke, G. J. te Meerman, R. H. Sijmons, M. A. Swertz, B. Sikkema-Raddatz
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/50fe59706dee446cb5379772bb6c48fa
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spelling	oai:doaj.org-article:50fe59706dee446cb5379772bb6c48fa2021-12-02T12:32:40ZNovel Algorithms for Improved Sensitivity in Non-Invasive Prenatal Testing10.1038/s41598-017-02031-52045-2322https://doaj.org/article/50fe59706dee446cb5379772bb6c48fa2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02031-5https://doaj.org/toc/2045-2322Abstract Non-invasive prenatal testing (NIPT) of cell-free DNA in maternal plasma, which is a mixture of maternal DNA and a low percentage of fetal DNA, can detect fetal aneuploidies using massively parallel sequencing. Because of the low percentage of fetal DNA, methods with high sensitivity and precision are required. However, sequencing variation lowers sensitivity and hampers detection of trisomy samples. Therefore, we have developed three algorithms to improve sensitivity and specificity: the chi-squared-based variation reduction (χ2VR), the regression-based Z-score (RBZ) and the Match QC score. The χ2VR reduces variability in sequence read counts per chromosome between samples, the RBZ allows for more precise trisomy prediction, and the Match QC score shows if the control group used is representative for a specific sample. We compared the performance of χ2VR to that of existing variation reduction algorithms (peak and GC correction) and that of RBZ to trisomy prediction algorithms (standard Z-score, normalized chromosome value and median-absolute-deviation-based Z-score). χ2VR and the RBZ both reduce variability more than existing methods, and thereby increase the sensitivity of the NIPT analysis. We found the optimal combination of algorithms was to use both GC correction and χ2VR for pre-processing and to use RBZ as the trisomy prediction method.L. F. JohanssonE. N. de BoerH. A. de WeerdF. van DijkM. G. ElferinkG. H. Schuring-BlomR. F. SuijkerbuijkR. J. SinkeG. J. te MeermanR. H. SijmonsM. A. SwertzB. Sikkema-RaddatzNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q L. F. Johansson E. N. de Boer H. A. de Weerd F. van Dijk M. G. Elferink G. H. Schuring-Blom R. F. Suijkerbuijk R. J. Sinke G. J. te Meerman R. H. Sijmons M. A. Swertz B. Sikkema-Raddatz Novel Algorithms for Improved Sensitivity in Non-Invasive Prenatal Testing
description	Abstract Non-invasive prenatal testing (NIPT) of cell-free DNA in maternal plasma, which is a mixture of maternal DNA and a low percentage of fetal DNA, can detect fetal aneuploidies using massively parallel sequencing. Because of the low percentage of fetal DNA, methods with high sensitivity and precision are required. However, sequencing variation lowers sensitivity and hampers detection of trisomy samples. Therefore, we have developed three algorithms to improve sensitivity and specificity: the chi-squared-based variation reduction (χ2VR), the regression-based Z-score (RBZ) and the Match QC score. The χ2VR reduces variability in sequence read counts per chromosome between samples, the RBZ allows for more precise trisomy prediction, and the Match QC score shows if the control group used is representative for a specific sample. We compared the performance of χ2VR to that of existing variation reduction algorithms (peak and GC correction) and that of RBZ to trisomy prediction algorithms (standard Z-score, normalized chromosome value and median-absolute-deviation-based Z-score). χ2VR and the RBZ both reduce variability more than existing methods, and thereby increase the sensitivity of the NIPT analysis. We found the optimal combination of algorithms was to use both GC correction and χ2VR for pre-processing and to use RBZ as the trisomy prediction method.
format	article
author	L. F. Johansson E. N. de Boer H. A. de Weerd F. van Dijk M. G. Elferink G. H. Schuring-Blom R. F. Suijkerbuijk R. J. Sinke G. J. te Meerman R. H. Sijmons M. A. Swertz B. Sikkema-Raddatz
author_facet	L. F. Johansson E. N. de Boer H. A. de Weerd F. van Dijk M. G. Elferink G. H. Schuring-Blom R. F. Suijkerbuijk R. J. Sinke G. J. te Meerman R. H. Sijmons M. A. Swertz B. Sikkema-Raddatz
author_sort	L. F. Johansson
title	Novel Algorithms for Improved Sensitivity in Non-Invasive Prenatal Testing
title_short	Novel Algorithms for Improved Sensitivity in Non-Invasive Prenatal Testing
title_full	Novel Algorithms for Improved Sensitivity in Non-Invasive Prenatal Testing
title_fullStr	Novel Algorithms for Improved Sensitivity in Non-Invasive Prenatal Testing
title_full_unstemmed	Novel Algorithms for Improved Sensitivity in Non-Invasive Prenatal Testing
title_sort	novel algorithms for improved sensitivity in non-invasive prenatal testing
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/50fe59706dee446cb5379772bb6c48fa
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Novel Algorithms for Improved Sensitivity in Non-Invasive Prenatal Testing

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