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Updated: Sep 28, 2025

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High-Selectivity Single-Nucleotide Variant Capture Technology Based on the DNA Reaction Network.

Weiyang Tang1,2, Yibin Zhang1, Jiachun Wang1

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A new technique called SCREEN specifically captures and enriches low-abundance single-nucleotide variants (SNVs) in nucleic acid samples. This method significantly boosts SNV detection for early disease diagnosis using liquid biopsies.

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Area of Science:

  • Molecular Biology
  • Genetics
  • Biotechnology

Background:

  • Extremely low abundance of circulating tumor DNA (ctDNA) in blood limits liquid biopsy development for early disease diagnosis.
  • Detecting rare single-nucleotide variants (SNVs) is crucial for sensitive molecular diagnostics.

Purpose of the Study:

  • To introduce and validate SCREEN, a novel DNA-based screening technique for specific capture and enrichment of low-abundance SNVs.
  • To demonstrate SCREEN's effectiveness in enhancing the detection sensitivity of ultralow abundance SNVs without selective amplification.

Main Methods:

  • Development of a DNA-responsive network (DRN)-based screening technique named SCREEN.
  • Application of SCREEN for specific capture and enrichment of SNV nucleic acid samples from highly homologous mixtures.
  • Evaluation of SCREEN's enrichment efficiency through multiple rounds of capture.

Main Results:

  • SCREEN achieved a 108-fold increase in SNV abundance from 0.01% to 1.08% in highly homologous mixtures.
  • Two rounds of SCREEN capture significantly increased SNV abundance from 0.1% to 51%.
  • SCREEN demonstrated powerful enhancement of next-generation sequencing (NGS) for ultralow abundance SNV detection.

Conclusions:

  • SCREEN is a highly effective pre-enrichment technique for ultralow abundance SNV detection.
  • The SCREEN technique shows high compatibility with existing molecular diagnostic methods.
  • SCREEN technology holds promise for advancing liquid biopsy applications in early disease diagnosis.