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

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.