Abstract

Next-generation DNA sequencing is currently limited by an inability to accurately count the number of input DNA molecules. Molecular counting is particularly needed when accurate quantification is required for diagnostic purposes, such as in single gene non-invasive prenatal testing (sgNIPT) and liquid biopsy. We developed Quantitative Counting Template (QCT) molecular counting to reconstruct the number of input DNA molecules using sequencing data. We then used QCT molecular counting to develop sgNIPTs of sickle cell disease, cystic fibrosis, spinal muscular atrophy, alpha-thalassemia, and beta-thalassemia. The analytical sensitivity and specificity of sgNIPT was >98% and >99%, respectively. Validation of sgNIPTs was further performed with maternal blood samples collected during pregnancy, and sgNIPTs were 100% concordant with newborn follow-up.

Details

Title
A novel high-throughput molecular counting method with single base-pair resolution enables accurate single-gene NIPT
Author
Tsao, David S 1 ; Sukrit Silas 2 ; Landry, Brian P 1 ; Itzep, Nelda P 3 ; Nguyen, Amy B 1 ; Greenberg, Samuel 1 ; Kanne, Celeste K 3 ; Sheehan, Vivien A 3 ; Sharma, Rani 4 ; Shukla, Rahul 5 ; Arora, Prem N 5 ; Atay, Oguzhan 1 

 BillionToOne Inc., Menlo Park, CA, USA 
 Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA 
 Department of Pediatrics, Division of Hematology/Oncology, Baylor College of Medicine, Houston, TX, United States 
 SeqIndia Labs Pvt. Ltd., New Delhi, India 
 Yashoda Super Speciality Hospitals, Ghaziabad, Uttar Pradesh, India 
Pages
1-14
Publication year
2019
Publication date
Oct 2019
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2301897691
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.