Institute of Molecular Medicine, Renji Hospital, School of Medicine , Shanghai Jiao Tong University , Shanghai 200127 , China.
State Key Laboratory for Physical Chemistry of Solid Surfaces, Key Laboratory for Chemical Biology of Fujian Province, Key Laboratory of Analytical Chemistry, and Department of Chemical Biology, College of Chemistry and Chemical Engineering , Xiamen University , Xiamen , 361005 , People's Republic of China.
Anal Chem. 2020 Feb 18;92(4):3307-3314. doi: 10.1021/acs.analchem.9b05203. Epub 2020 Jan 8.
Molecular recognition ligands are of great significance in many fields, but our ability to develop new recognition molecules remains to be expanded. Here, we developed a Sequential Multidimensional Analysis algoRiThm for aptamer discovery (SMART-Aptamer) from high-throughput sequencing (HTS) data of SELEX libraries based on multilevel structure analysis and unsupervised machine learning to discover nucleic acid recognition ligands with high accuracy and efficiency. We validated SMART-Aptamer with three sets of HTS data from screening pools against hESCs, EpCAM, and CSV. High affinity aptamers for all three targets were successfully obtained, and the results revealed that SMART-Aptamer is able to pick out high affinity aptamers with low false positive and negative rates. With the advantages of accuracy, efficiency, and robustness, SMART-Aptamer represents a paradigm-shift strategy for the discovery of binding ligands for a variety of biomedical applications.
分子识别配体在许多领域都具有重要意义，但我们开发新识别分子的能力还有待提高。在这里，我们基于多层次结构分析和无监督机器学习，开发了一种从 SELEX 文库高通量测序 (HTS) 数据中发现适体的序贯多维分析算法 (SMART-Aptamer)，以高精度和高效率发现核酸识别配体。我们使用针对 hESCs、EpCAM 和 CSV 的三种 HTS 筛选池数据对 SMART-Aptamer 进行了验证。成功获得了所有三个靶标的高亲和力适体，结果表明 SMART-Aptamer 能够以低假阳性和假阴性率挑选出高亲和力适体。SMART-Aptamer 具有准确性、效率和稳健性的优势，代表了一种用于发现各种生物医学应用结合配体的突破性策略。
