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

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.