Logical Analysis of Multiple Single-Nucleotide-Polymorphisms with Programmable DNA Molecular Computation for Clinical Diagnostics

Angew Chem Int Ed Engl. 2022 Apr 4;61(15):e202117658. doi: 10.1002/anie.202117658. Epub 2022 Feb 16.

Abstract

Analyzing complex single-nucleotide-polymorphism (SNP) combinations in the genome is important for research and clinical applications, given that different SNP combinations can generate different phenotypic consequences. Recent works have shown that DNA-based molecular computing is powerful for simultaneously sensing and analyzing complex molecular information. Here, we designed a switching circuit-based DNA computational scheme that can integrate the sensing of multiple SNPs and simultaneously perform logical analysis of the detected SNP information to directly report clinical outcomes. As a demonstration, we successfully achieved automatic and accurate identification of 21 different blood group genotypes from 83 clinical blood samples with 100 % accuracy compared to sequencing data in a more rapid manner (3 hours). Our method enables a new mode of automatic and logical sensing and analyzing subtle molecular information for clinical diagnosis, as well as guiding personalized medication.

Keywords: Blood Group; DNA Molecular Computation; Genotyping; Logical Analysis; Single Nucleotide Polymorphism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computers, Molecular*
  • DNA / genetics
  • Genotype
  • Nucleotides
  • Polymorphism, Single Nucleotide*
  • Sequence Analysis, DNA

Substances

  • Nucleotides
  • DNA