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Combination of Fetal Fraction Estimators Based on Fragment Lengths and Fragment Counts in Non-Invasive Prenatal Testing

The reliability of non-invasive prenatal testing is highly dependent on accurate estimation of fetal fraction. Several methods have been proposed up to date, utilizing different attributes of analyzed genomic material, for example length and genomic location of sequenced DNA fragments. These two sou...

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Autores principales: Gazdarica, Juraj, Hekel, Rastislav, Budis, Jaroslav, Kucharik, Marcel, Duris, Frantisek, Radvanszky, Jan, Turna, Jan, Szemes, Tomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6719007/
https://www.ncbi.nlm.nih.gov/pubmed/31416246
http://dx.doi.org/10.3390/ijms20163959
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author Gazdarica, Juraj
Hekel, Rastislav
Budis, Jaroslav
Kucharik, Marcel
Duris, Frantisek
Radvanszky, Jan
Turna, Jan
Szemes, Tomas
author_facet Gazdarica, Juraj
Hekel, Rastislav
Budis, Jaroslav
Kucharik, Marcel
Duris, Frantisek
Radvanszky, Jan
Turna, Jan
Szemes, Tomas
author_sort Gazdarica, Juraj
collection PubMed
description The reliability of non-invasive prenatal testing is highly dependent on accurate estimation of fetal fraction. Several methods have been proposed up to date, utilizing different attributes of analyzed genomic material, for example length and genomic location of sequenced DNA fragments. These two sources of information are relatively unrelated, but so far, there have been no published attempts to combine them to get an improved predictor. We collected 2454 single euploid male fetus samples from women undergoing NIPT testing. Fetal fractions were calculated using several proposed predictors and the state-of-the-art SeqFF method. Predictions were compared with the reference Y-based method. We demonstrate that prediction based on length of sequenced DNA fragments may achieve nearly the same precision as the state-of-the-art methods based on their genomic locations. We also show that combination of several sample attributes leads to a predictor that has superior prediction accuracy over any single approach. Finally, appropriate weighting of samples in the training process may achieve higher accuracy for samples with low fetal fraction and so allow more reliability for subsequent testing for genomic aberrations. We propose several improvements in fetal fraction estimation with a special focus on the samples most prone to wrong conclusion.
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spelling pubmed-67190072019-09-10 Combination of Fetal Fraction Estimators Based on Fragment Lengths and Fragment Counts in Non-Invasive Prenatal Testing Gazdarica, Juraj Hekel, Rastislav Budis, Jaroslav Kucharik, Marcel Duris, Frantisek Radvanszky, Jan Turna, Jan Szemes, Tomas Int J Mol Sci Article The reliability of non-invasive prenatal testing is highly dependent on accurate estimation of fetal fraction. Several methods have been proposed up to date, utilizing different attributes of analyzed genomic material, for example length and genomic location of sequenced DNA fragments. These two sources of information are relatively unrelated, but so far, there have been no published attempts to combine them to get an improved predictor. We collected 2454 single euploid male fetus samples from women undergoing NIPT testing. Fetal fractions were calculated using several proposed predictors and the state-of-the-art SeqFF method. Predictions were compared with the reference Y-based method. We demonstrate that prediction based on length of sequenced DNA fragments may achieve nearly the same precision as the state-of-the-art methods based on their genomic locations. We also show that combination of several sample attributes leads to a predictor that has superior prediction accuracy over any single approach. Finally, appropriate weighting of samples in the training process may achieve higher accuracy for samples with low fetal fraction and so allow more reliability for subsequent testing for genomic aberrations. We propose several improvements in fetal fraction estimation with a special focus on the samples most prone to wrong conclusion. MDPI 2019-08-14 /pmc/articles/PMC6719007/ /pubmed/31416246 http://dx.doi.org/10.3390/ijms20163959 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gazdarica, Juraj
Hekel, Rastislav
Budis, Jaroslav
Kucharik, Marcel
Duris, Frantisek
Radvanszky, Jan
Turna, Jan
Szemes, Tomas
Combination of Fetal Fraction Estimators Based on Fragment Lengths and Fragment Counts in Non-Invasive Prenatal Testing
title Combination of Fetal Fraction Estimators Based on Fragment Lengths and Fragment Counts in Non-Invasive Prenatal Testing
title_full Combination of Fetal Fraction Estimators Based on Fragment Lengths and Fragment Counts in Non-Invasive Prenatal Testing
title_fullStr Combination of Fetal Fraction Estimators Based on Fragment Lengths and Fragment Counts in Non-Invasive Prenatal Testing
title_full_unstemmed Combination of Fetal Fraction Estimators Based on Fragment Lengths and Fragment Counts in Non-Invasive Prenatal Testing
title_short Combination of Fetal Fraction Estimators Based on Fragment Lengths and Fragment Counts in Non-Invasive Prenatal Testing
title_sort combination of fetal fraction estimators based on fragment lengths and fragment counts in non-invasive prenatal testing
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6719007/
https://www.ncbi.nlm.nih.gov/pubmed/31416246
http://dx.doi.org/10.3390/ijms20163959
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