Phosphorylated protein chip combined with artificial intelligence tools for precise drug screeningOA
We have developed a protein array system,named"Phospho-Totum",which reproduces the phosphorylation state of a sample on the array.The protein array contains 1471 proteins from 273 known signaling pathways.According to the activation degrees of tyrosine kinases in the sample,the corresponding groups of substrate proteins on the array are phosphorylated under the same conditions.In addition to measuring the phosphorylation levels of the 1471 substrates,we have developed and performed the artificial intelligence-assisted tools to further characterize the phosphorylation state and estimate pathway activation,tyrosine kinase activation,and a list of kinase inhibitors that produce phosphorylation states similar to that of the sample.The Phospho-Totum system,which seamlessly links and interrogates the measurements and analyses,has the potential to not only elucidate pathophysiological mechanisms in diseases by reproducing the phosphorylation state of samples,but also be useful for drug discovery,particularly for screening targeted kinases for potential drug kinase inhibitors.
Katsuhisa Horimoto;Yuki Suyama;Tadamasa Sasaki;Kazuhiko Fukui;Lili Feng;Meiling Sun;Yamin Tang;Yixuan Zhang;Dongyin Chen;Feng Han;
SOCIUM Inc.,Tokyo 1350064,Japan International Medical Center,Saitama Medical University,Saitama 350-1298,Japan Artificial Intelligence Research Center,National Institute of Advanced Industrial Science and Technology,Tokyo 1350064,JapanSOCIUM Inc.,Tokyo 1350064,JapanDepartment of Informatics and Data Science,Sanyo-Onoda City University,Yamaguchi 7560884,JapanInternational Joint Laboratory for Drug Target of Critical Illnesses,School of Pharmacy,Nanjing Medical University,Nanjing,Jiangsu 211166,ChinaDepartment of Physiology,School of Basic Medical Sciences,Nanjing Medical University,Nanjing,Jiangsu 211166,ChinaGusu School,Nanjing Medical University,Suzhou,Jiangsu 215001,ChinaInternational Joint Laboratory for Drug Target of Critical Illnesses,School of Pharmacy,Nanjing Medical University,Nanjing,Jiangsu 211166,China Gusu School,Nanjing Medical University,Suzhou,Jiangsu 215001,China National Vaccine Innovation Platform,Nanjing Medical University,Nanjing,Jiangsu 211166,China
电子信息工程
Phospho-Totumprotein arraysignal transduction pathwaysartificial intelligence toolsdrug screening
《Journal of Biomedical Research》 2024 (003)
P.195-205 / 11
supported by the State Key Program of National Natural Science Foundation of China(Grant No.82230114 to F.H.);the National Key Research and Development Program of China(Grant No.2022YFE0104800 to F.H.).
评论