Improving the accuracy of noninvasive prenatal testing through size‐selection between fetal and maternal cfDNA

Prenatal DiagnosisVolume 43, Issue 13 p. 1581-1592 ORIGINAL ARTICLE Improving the accuracy of noninvasive prenatal testing through size-selection between fetal and maternal cfDNA Hyuk-Jung Kwon, Hyuk-Jung Kwon orcid.org/0000-0001-7005-6999 R&D Department, Eone-Diagnomics Genome Center, Incheon, Republic of KoreaSearch for more papers by this authorSeonyoung Yun, Seonyoung Yun R&D Department, Eone-Diagnomics Genome Center, Incheon, Republic of KoreaSearch for more papers by this authorJoungsu Joo, Joungsu Joo R&D Department, Eone-Diagnomics Genome Center, Incheon, Republic of KoreaSearch for more papers by this authorDabin Park, Dabin Park R&D Department, Eone-Diagnomics Genome Center, Incheon, Republic of KoreaSearch for more papers by this authorWoo-Jung Do, Woo-Jung Do R&D Department, Eone-Diagnomics Genome Center, Incheon, Republic of KoreaSearch for more papers by this authorSunghoon Lee, Sunghoon Lee R&D Department, Eone-Diagnomics Genome Center, Incheon, Republic of KoreaSearch for more papers by this authorMin-Seob Lee, Corresponding Author Min-Seob Lee [email protected] R&D Department, Eone-Diagnomics Genome Center, Incheon, Republic of Korea Diagnomics, San Diego, California, USA Correspondence Min-Seob Lee, Eone-Diagnomics Genome Center, Inc., 143 Gaetbeol-ro, Yeonsu-gu, Incheon 21999, Republic of Korea. Email: [email protected]Search for more papers by this author Hyuk-Jung Kwon, Hyuk-Jung Kwon orcid.org/0000-0001-7005-6999 R&D Department, Eone-Diagnomics Genome Center, Incheon, Republic of KoreaSearch for more papers by this authorSeonyoung Yun, Seonyoung Yun R&D Department, Eone-Diagnomics Genome Center, Incheon, Republic of KoreaSearch for more papers by this authorJoungsu Joo, Joungsu Joo R&D Department, Eone-Diagnomics Genome Center, Incheon, Republic of KoreaSearch for more papers by this authorDabin Park, Dabin Park R&D Department, Eone-Diagnomics Genome Center, Incheon, Republic of KoreaSearch for more papers by this authorWoo-Jung Do, Woo-Jung Do R&D Department, Eone-Diagnomics Genome Center, Incheon, Republic of KoreaSearch for more papers by this authorSunghoon Lee, Sunghoon Lee R&D Department, Eone-Diagnomics Genome Center, Incheon, Republic of KoreaSearch for more papers by this authorMin-Seob Lee, Corresponding Author Min-Seob Lee [email protected] R&D Department, Eone-Diagnomics Genome Center, Incheon, Republic of Korea Diagnomics, San Diego, California, USA Correspondence Min-Seob Lee, Eone-Diagnomics Genome Center, Inc., 143 Gaetbeol-ro, Yeonsu-gu, Incheon 21999, Republic of Korea. Email: [email protected]Search for more papers by this author First published: 17 November 2023 https://doi.org/10.1002/pd.6464Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Abstract Objectives In general, fetal cfDNA is shorter than maternal cfDNA, and accuracy of noninvasive prenatal testing (NIPT) results can be improved by selecting shorter cfDNA fragments to enrich fetal-derived cfDNA. This study investigated potential improvements in the accuracy of NIPT by performing classification and analysis based on differences in cfDNA size. Methods We performed paired-end sequencing to identify size ranges of fetal and maternal cfDNA from 62,374 pregnant women. We then developed a size-selection method to isolate and analyze both fetal and maternal cfDNA, defining fetal-derived cfDNA as less than 150 bp and maternal-derived cfDNA as greater than 180 bp. Results By implementing size-selection method, the accuracy of NIPT was improved, resulting in an increase in the overall positive predictive value for all aneuploidies from 89.57% to 97.1%. This was achieved by enriching both fetal and maternal-derived cfDNA, which increased fetal DNA fraction while the number of false positives for all aneuploidies was reduced by more than 70%. Conclusions We identified the differences in read length between fetal and maternal-derived cfDNA, and selectively enriched both shorter and longer cfDNA fragments for subsequent analysis. Our approach can increase the detection accuracy of NIPT for detecting fetal aneuploidies and reduce the number of false positives caused by maternal chromosomal abnormalities. CONFLICT OF INTEREST STATEMENT All authors declare that there are no conflicts of interest. Open Research DATA AVAILABILITY STATEMENT Data sharing is not applicable to this article as no new data were created or analyzed in this study. Supporting Information Filename Description pd6464-sup-0001-suppl-data.docx231.1 KB Supporting Information S1 Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. 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