Dataset Information

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 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 (?²VR), the regression-based Z-score (RBZ) and the Match QC score. The ?²VR 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 ?²VR 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). ?²VR 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 ?²VR for pre-processing and to use RBZ as the trisomy prediction method.

SUBMITTER: Johansson LF

PROVIDER: S-EPMC5431782 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Novel Algorithms for Improved Sensitivity in Non-Invasive Prenatal Testing.

Johansson L F LF de Boer E N EN de Weerd H A HA van Dijk F F Elferink M G MG Schuring-Blom G H GH Suijkerbuijk R F RF Sinke R J RJ Te Meerman G J GJ Sijmons R H RH Swertz M A MA Sikkema-Raddatz B B

Scientific reports 20170512 1

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-sq ...[more]

PMID: 28500333

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Project description:ObjectiveNon-invasive prenatal testing (NIPT) is a front-line screening for fatal chromosomal aneuploidy. In pregnant women with a risk of having fetal congenital disorders, NIPT is anticipated to reduce the needs of invasive prenatal diagnostic test (IPD). The objective of this study was to understand the acceptance of NIPT and the utility of NIPT to mitigate concerns about IPD in the US high-risk pregnancy management.Design and settingThis was a retrospective observational research using healthcare records obtained from an academic healthcare system in the US. The study consisted of site-level longitudinal analysis and patient-level cross-sectional analysis.ParticipantA total of 5660 new high-risk pregnancies with age ≥35 years were identified for the longitudinal trend analysis. Cross-sectional utility assessment included 2057 pregnant women.Exposure and outcome measuresLongitudinal trends of NIPT order, IPD procedure and the number of patients diagnosed with high-risk pregnancy were descriptively summarised. In the cross-sectional assessment, we tested the association between the use of NIPT and IPD using multivariable regression.ResultsThe rate of increase in the NIPT use exceeded the changes in the number of high-risk pregnancies with age ≥35 years, while the number of annual IPD procedures has fluctuated without specific trends. There was no significant association between the numbers of NIPT and IPD with the adjusted ORs between 0.90 and 1.14 (p>0.1). The order of NIPT was not selected as an independent variable predicting the use of IPD. Clinical characteristics indicating low socioeconomic status and limited healthcare coverage are associated with less use of NIPT and lower clinical utility.ConclusionAlthough prenatal care accepted NIPT over the last decade, the utility of NIPT in mitigating concerns on IPD is unclear and needs further investigation. Limited clinical utility should be addressed in the context of disparity in prenatal care.

Dataset Information

Novel Algorithms for Improved Sensitivity in Non-Invasive Prenatal Testing.

Publications

Novel Algorithms for Improved Sensitivity in Non-Invasive Prenatal Testing.

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