Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, State Key Laboratory of Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
Department of Laboratory Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 201306, China.
Angew Chem Int Ed Engl. 2022 Apr 4;61(15):e202117658. doi: 10.1002/anie.202117658. Epub 2022 Feb 16.
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.
分析基因组中复杂的单核苷酸多态性 (SNP) 组合对于研究和临床应用非常重要，因为不同的 SNP 组合可能会产生不同的表型后果。最近的研究表明，基于 DNA 的分子计算对于同时感测和分析复杂的分子信息非常有效。在这里，我们设计了一种基于开关电路的 DNA 计算方案，该方案可以集成对多个 SNP 的感测，并同时对检测到的 SNP 信息进行逻辑分析，从而直接报告临床结果。作为一个演示，我们成功地从 83 个临床血液样本中自动且准确地识别出 21 种不同的血型基因型，与测序数据相比，速度更快（3 小时），准确率为 100%。我们的方法为临床诊断以及指导个性化药物治疗提供了一种新的自动逻辑感测和分析微妙分子信息的模式。
