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Performance of the neoBona test: a new paired-end massively parallel shotgun sequencing approach for cell-free DNA-based aneuploidy screening.
Ultrasound Obstet Gynecol 2017; 49(4):460-464UO

Abstract

OBJECTIVE

To assess the performance of screening for fetal trisomies 21, 18 and 13 by cell-free (cf) DNA analysis of maternal blood using a new method based on paired-end massively parallel shotgun sequencing (MPSS).

METHODS

This was a blinded study of plasma samples (1mL) obtained from 1000 women undergoing screening for fetal trisomies 21, 18 and 13 at 11-13 weeks' gestation. The study included 50 cases with confirmed fetal trisomy 21, 30 with trisomy 18, 10 with trisomy 13 and 910 unaffected pregnancies. Paired-end MPSS with the neoBona® test allowed simultaneous assessment of fetal fraction, cfDNA fragment size distribution and chromosome counting, which were integrated into a new analysis algorithm to calculate trisomy likelihood ratios (t-score) for each chromosome of interest. Each sample was classified as trisomic or unaffected using chromosome-specific cut-offs set at t-score values of 1.5 for trisomy 21 and 3.0 for trisomies 18 and 13.

RESULTS

Valid results were provided for 988 (98.8%) cases; 12 (1.2%) samples, from nine euploid and three trisomy 21 pregnancies, did not pass quality-control criteria and were excluded from further analysis. All 47 cases of trisomy 21, all 10 of trisomy 13, 29 of 30 with trisomy 18 and all 901 unaffected cases were classified correctly. Median fetal fraction was 10.5% (range, 0.3-33.8%) and trisomic and unaffected cases with low fetal fractions of < 1% were identified correctly.

CONCLUSIONS

This novel method for cfDNA analysis of maternal plasma, which utilizes paired-end MPSS, can provide accurate prediction of fetal trisomies. Use of a new multicomponent t-score removes the need to reject samples with fetal fraction < 4%, which potentially extends the benefits of non-invasive prenatal cfDNA analysis to a larger proportion of pregnancies. © 2016 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Authors+Show Affiliations

Department of Molecular Genetics, Labco Diagnostics, SYNLAB Group, Barcelona, Spain.Department of Molecular Genetics, Labco Diagnostics, SYNLAB Group, Barcelona, Spain.Department of Molecular Genetics, Labco Diagnostics, SYNLAB Group, Barcelona, Spain.Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK.Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27981672

Citation

Cirigliano, V, et al. "Performance of the neoBona Test: a New Paired-end Massively Parallel Shotgun Sequencing Approach for Cell-free DNA-based Aneuploidy Screening." Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology, vol. 49, no. 4, 2017, pp. 460-464.
Cirigliano V, Ordoñez E, Rueda L, et al. Performance of the neoBona test: a new paired-end massively parallel shotgun sequencing approach for cell-free DNA-based aneuploidy screening. Ultrasound Obstet Gynecol. 2017;49(4):460-464.
Cirigliano, V., Ordoñez, E., Rueda, L., Syngelaki, A., & Nicolaides, K. H. (2017). Performance of the neoBona test: a new paired-end massively parallel shotgun sequencing approach for cell-free DNA-based aneuploidy screening. Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology, 49(4), pp. 460-464. doi:10.1002/uog.17386.
Cirigliano V, et al. Performance of the neoBona Test: a New Paired-end Massively Parallel Shotgun Sequencing Approach for Cell-free DNA-based Aneuploidy Screening. Ultrasound Obstet Gynecol. 2017;49(4):460-464. PubMed PMID: 27981672.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Performance of the neoBona test: a new paired-end massively parallel shotgun sequencing approach for cell-free DNA-based aneuploidy screening. AU - Cirigliano,V, AU - Ordoñez,E, AU - Rueda,L, AU - Syngelaki,A, AU - Nicolaides,K H, Y1 - 2017/02/28/ PY - 2016/09/16/received PY - 2016/11/29/revised PY - 2016/12/09/accepted PY - 2016/12/17/pubmed PY - 2017/9/19/medline PY - 2016/12/17/entrez KW - cell-free DNA KW - paired-end sequencing KW - screening KW - trisomy SP - 460 EP - 464 JF - Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology JO - Ultrasound Obstet Gynecol VL - 49 IS - 4 N2 - OBJECTIVE: To assess the performance of screening for fetal trisomies 21, 18 and 13 by cell-free (cf) DNA analysis of maternal blood using a new method based on paired-end massively parallel shotgun sequencing (MPSS). METHODS: This was a blinded study of plasma samples (1mL) obtained from 1000 women undergoing screening for fetal trisomies 21, 18 and 13 at 11-13 weeks' gestation. The study included 50 cases with confirmed fetal trisomy 21, 30 with trisomy 18, 10 with trisomy 13 and 910 unaffected pregnancies. Paired-end MPSS with the neoBona® test allowed simultaneous assessment of fetal fraction, cfDNA fragment size distribution and chromosome counting, which were integrated into a new analysis algorithm to calculate trisomy likelihood ratios (t-score) for each chromosome of interest. Each sample was classified as trisomic or unaffected using chromosome-specific cut-offs set at t-score values of 1.5 for trisomy 21 and 3.0 for trisomies 18 and 13. RESULTS: Valid results were provided for 988 (98.8%) cases; 12 (1.2%) samples, from nine euploid and three trisomy 21 pregnancies, did not pass quality-control criteria and were excluded from further analysis. All 47 cases of trisomy 21, all 10 of trisomy 13, 29 of 30 with trisomy 18 and all 901 unaffected cases were classified correctly. Median fetal fraction was 10.5% (range, 0.3-33.8%) and trisomic and unaffected cases with low fetal fractions of < 1% were identified correctly. CONCLUSIONS: This novel method for cfDNA analysis of maternal plasma, which utilizes paired-end MPSS, can provide accurate prediction of fetal trisomies. Use of a new multicomponent t-score removes the need to reject samples with fetal fraction < 4%, which potentially extends the benefits of non-invasive prenatal cfDNA analysis to a larger proportion of pregnancies. © 2016 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. SN - 1469-0705 UR - https://www.unboundmedicine.com/medline/citation/27981672/Performance_of_the_neoBona_test:_a_new_paired_end_massively_parallel_shotgun_sequencing_approach_for_cell_free_DNA_based_aneuploidy_screening_ L2 - https://doi.org/10.1002/uog.17386 DB - PRIME DP - Unbound Medicine ER -