We quantify the mean potential energy of a passive colloidal particle harmonically confined in a bacterial solution using optical traps.We find that the average potential energy of the passive particle depends on the ...We quantify the mean potential energy of a passive colloidal particle harmonically confined in a bacterial solution using optical traps.We find that the average potential energy of the passive particle depends on the trap stiffness,in contrast to the equilibrium case where energy partition is independent of the external constraints.The constraint dependence of the mean potential energy originates from the fact that the persistent collisions between the passive particle and the active bacteria are influenced by the particle relaxation dynamics.Our experimental results are consistent with the Brownian dynamics simulations,and confirm the recent theoretical prediction.展开更多
Base editing technology is being increasingly applied in genome engineering,but the current strategy for designing guide RNAs(gRNAs)relies substantially on empirical experience rather than a dependable and efficient i...Base editing technology is being increasingly applied in genome engineering,but the current strategy for designing guide RNAs(gRNAs)relies substantially on empirical experience rather than a dependable and efficient in silico design.Furthermore,the pleiotropic effect of base editing on disease treatment remains unexplored,which prevents its further clinical usage.Here,we presented BExplorer,an integrated and comprehensive computational pipeline to optimize the design of gRNAs for 26 existing types of base editors in silico.Using BExplorer,we described its results for two types of mainstream base editors,BE3 and ABE7.10,and evaluated the pleiotropic effects of the corresponding base editing loci.BExplorer revealed 524 and 900 editable pathogenic single nucleotide polymorphism(SNP)loci in the human genome together with the selected optimized gRNAs for BE3 and ABE7.10,respectively.In addition,the impact of 707 edited pathogenic SNP loci following base editing on 131 diseases was systematically explored by revealing their pleiotropic effects,indicating that base editing should be carefully utilized given the potential pleiotropic effects.Collectively,the systematic exploration of optimized base editing gRNA design and the corresponding pleiotropic effects with BExplorer provides a computational basis for applying base editing in disease treatment.展开更多
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11874397,11674365,11774393,and 11774394).
文摘We quantify the mean potential energy of a passive colloidal particle harmonically confined in a bacterial solution using optical traps.We find that the average potential energy of the passive particle depends on the trap stiffness,in contrast to the equilibrium case where energy partition is independent of the external constraints.The constraint dependence of the mean potential energy originates from the fact that the persistent collisions between the passive particle and the active bacteria are influenced by the particle relaxation dynamics.Our experimental results are consistent with the Brownian dynamics simulations,and confirm the recent theoretical prediction.
基金supported by the National Key R&D Program of China(Grant No.2021YFF1201200)the National Natural Science Foundation of China(Grant Nos.31970638 and 61572361)+2 种基金the Shanghai Natural Science Foundation Program(Grant No.17ZR1449400)the Shanghai Artificial Intelligence Technology Standard Project(Grant No.19DZ2200900)the Shanghai Shuguang scholars project,the WeBank scholars project,and the Fundamental Research Funds for the Central Universities.
文摘Base editing technology is being increasingly applied in genome engineering,but the current strategy for designing guide RNAs(gRNAs)relies substantially on empirical experience rather than a dependable and efficient in silico design.Furthermore,the pleiotropic effect of base editing on disease treatment remains unexplored,which prevents its further clinical usage.Here,we presented BExplorer,an integrated and comprehensive computational pipeline to optimize the design of gRNAs for 26 existing types of base editors in silico.Using BExplorer,we described its results for two types of mainstream base editors,BE3 and ABE7.10,and evaluated the pleiotropic effects of the corresponding base editing loci.BExplorer revealed 524 and 900 editable pathogenic single nucleotide polymorphism(SNP)loci in the human genome together with the selected optimized gRNAs for BE3 and ABE7.10,respectively.In addition,the impact of 707 edited pathogenic SNP loci following base editing on 131 diseases was systematically explored by revealing their pleiotropic effects,indicating that base editing should be carefully utilized given the potential pleiotropic effects.Collectively,the systematic exploration of optimized base editing gRNA design and the corresponding pleiotropic effects with BExplorer provides a computational basis for applying base editing in disease treatment.
