Detection of Embryonic Trisomy 21 in the First Trimester Using Maternal Plasma Cell-Free RNA
Prenatal trisomy 21 (T21) screening commonly involves testing a maternal blood sample for fetal DNA aneuploidy. It is reliable but poses a cost barrier to universal screening. We hypothesized maternal plasma RNA screening might provide similar reliability but at a lower cost. Discovery experiments u...
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| Format: | Article |
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MDPI AG
2022-06-01
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| Series: | Diagnostics |
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| Online Access: | https://www.mdpi.com/2075-4418/12/6/1410 |
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| author | Carl P. Weiner Mark L. Weiss Helen Zhou Argyro Syngelaki Kypros H. Nicolaides Yafeng Dong |
| author_facet | Carl P. Weiner Mark L. Weiss Helen Zhou Argyro Syngelaki Kypros H. Nicolaides Yafeng Dong |
| author_sort | Carl P. Weiner |
| collection | DOAJ |
| description | Prenatal trisomy 21 (T21) screening commonly involves testing a maternal blood sample for fetal DNA aneuploidy. It is reliable but poses a cost barrier to universal screening. We hypothesized maternal plasma RNA screening might provide similar reliability but at a lower cost. Discovery experiments used plasma cell-free RNA from 20 women 11–13 weeks tested by RNA and miRNA microarrays followed by qRT-PCR. Thirty-six mRNAs and 18 small RNAs of the discovery cDNA were identified by qPCR as potential markers of embryonic T21. The second objective was validation of the RNA predictors in 998 independent pregnancies at 11–13 weeks including 50 T21. Initial analyses identified 9–15 differentially expressed RNA with modest predictive power (AUC < 0.70). The 54 RNAs were then subjected to machine learning. Eleven algorithms were trained on one partition and tested on an independent partition. The three best algorithms were identified by Kappa score and the effects of training/testing partition size and dataset class imbalance on prediction were evaluated. Six to ten RNAs predicted T21 with AUCs up to 1.00. The findings suggest that maternal plasma collected at 11–13 weeks, tested by qRT-PCR, and classified by machine learning, may accurately predict T21 for a lower cost than plasma DNA, thus opening the door to universal screening. |
| first_indexed | 2024-03-10T00:00:20Z |
| format | Article |
| id | doaj.art-610f593f25e04ddda8060ce9af0987ad |
| institution | Directory Open Access Journal |
| issn | 2075-4418 |
| language | English |
| last_indexed | 2024-03-10T00:00:20Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Diagnostics |
| spelling | doaj.art-610f593f25e04ddda8060ce9af0987ad2023-11-23T16:17:41ZengMDPI AGDiagnostics2075-44182022-06-01126141010.3390/diagnostics12061410Detection of Embryonic Trisomy 21 in the First Trimester Using Maternal Plasma Cell-Free RNACarl P. Weiner0Mark L. Weiss1Helen Zhou2Argyro Syngelaki3Kypros H. Nicolaides4Yafeng Dong5Departments of Obstetrics and Gynecology and Molecular and Integrative Physiology, University of Kansas School of Medicine, Kansas City, KS 66160, USADepartments of Anatomy and Physiology & Midwest Institute of Comparative Stem Cell Biology, Kansas State University, Manhattan, KS 66506, USADepartments of Obstetrics and Gynecology and Molecular and Integrative Physiology, University of Kansas School of Medicine, Kansas City, KS 66160, USAFetal Medicine Research Institute, King’s College Hospital, London SE5 9RS, UKFetal Medicine Research Institute, King’s College Hospital, London SE5 9RS, UKRosetta Signaling Laboratory, Phoenix, AZ 85018, USAPrenatal trisomy 21 (T21) screening commonly involves testing a maternal blood sample for fetal DNA aneuploidy. It is reliable but poses a cost barrier to universal screening. We hypothesized maternal plasma RNA screening might provide similar reliability but at a lower cost. Discovery experiments used plasma cell-free RNA from 20 women 11–13 weeks tested by RNA and miRNA microarrays followed by qRT-PCR. Thirty-six mRNAs and 18 small RNAs of the discovery cDNA were identified by qPCR as potential markers of embryonic T21. The second objective was validation of the RNA predictors in 998 independent pregnancies at 11–13 weeks including 50 T21. Initial analyses identified 9–15 differentially expressed RNA with modest predictive power (AUC < 0.70). The 54 RNAs were then subjected to machine learning. Eleven algorithms were trained on one partition and tested on an independent partition. The three best algorithms were identified by Kappa score and the effects of training/testing partition size and dataset class imbalance on prediction were evaluated. Six to ten RNAs predicted T21 with AUCs up to 1.00. The findings suggest that maternal plasma collected at 11–13 weeks, tested by qRT-PCR, and classified by machine learning, may accurately predict T21 for a lower cost than plasma DNA, thus opening the door to universal screening.https://www.mdpi.com/2075-4418/12/6/1410pregnancytrisomy 21aneuploidyantenatal screeningantenatal diagnosisplasma transcriptome |
| spellingShingle | Carl P. Weiner Mark L. Weiss Helen Zhou Argyro Syngelaki Kypros H. Nicolaides Yafeng Dong Detection of Embryonic Trisomy 21 in the First Trimester Using Maternal Plasma Cell-Free RNA Diagnostics pregnancy trisomy 21 aneuploidy antenatal screening antenatal diagnosis plasma transcriptome |
| title | Detection of Embryonic Trisomy 21 in the First Trimester Using Maternal Plasma Cell-Free RNA |
| title_full | Detection of Embryonic Trisomy 21 in the First Trimester Using Maternal Plasma Cell-Free RNA |
| title_fullStr | Detection of Embryonic Trisomy 21 in the First Trimester Using Maternal Plasma Cell-Free RNA |
| title_full_unstemmed | Detection of Embryonic Trisomy 21 in the First Trimester Using Maternal Plasma Cell-Free RNA |
| title_short | Detection of Embryonic Trisomy 21 in the First Trimester Using Maternal Plasma Cell-Free RNA |
| title_sort | detection of embryonic trisomy 21 in the first trimester using maternal plasma cell free rna |
| topic | pregnancy trisomy 21 aneuploidy antenatal screening antenatal diagnosis plasma transcriptome |
| url | https://www.mdpi.com/2075-4418/12/6/1410 |
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