A novel high-throughput molecular counting method with single base-pair resolution enables accurate single-gene NIPT

David S. Tsao, Sukrit Silas, Brian P. Landry, Nelda P. Itzep, Amy B. Nguyen, Samuel Greenberg, Celeste K. Kanne, Vivien A. Sheehan, Rani Sharma, Rahul Shukla, Prem N. Arora, Oguzhan Atay

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

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.

Original languageEnglish (US)
Article number14382
JournalScientific reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019
Externally publishedYes

ASJC Scopus subject areas

  • General

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