Deep learning(DL)is currently revolutionizing peptide drug development due to both computational advances and the substantial recent expansion of digitized biological data.However,progress in oligopeptide drug develop...Deep learning(DL)is currently revolutionizing peptide drug development due to both computational advances and the substantial recent expansion of digitized biological data.However,progress in oligopeptide drug development has been limited,likely due to the lack of suitable datasets and difficulty in identifying informative features to use as inputs for DL models.Here,we utilized an unsupervised deep learning model to learn a semantic pattern based on the intrinsically disordered regions of~171 known osteogenic proteins.Subsequently,oligopeptides were generated from this semantic pattern based on Monte Carlo simulation,followed by in vivo functional characterization.A five amino acid oligopeptide(AIB5P)had strong bone-formation-promoting effects,as determined in multiple mouse models(e.g.,osteoporosis,fracture,and osseointegration of implants).Mechanistically,we showed that AIB5P promotes osteogenesis by binding to the integrinα5 subunit and thereby activating FAK signaling.In summary,we successfully established an oligopeptide discovery strategy based on a DL model and demonstrated its utility from cytological screening to animal experimental verification.展开更多
OSTEOKINES IN INTER-ORGAN COMMUNICATIONS The concept of“organic wholeness”permeates all the fields of traditional Chinese medicine,which is also widely accepted by modern medicine.The wealth of knowledge regarding i...OSTEOKINES IN INTER-ORGAN COMMUNICATIONS The concept of“organic wholeness”permeates all the fields of traditional Chinese medicine,which is also widely accepted by modern medicine.The wealth of knowledge regarding inter-organ communications generated in the latest decades provided solid evidence that human physiology and pathophysiology involve systematic interactions between multiple organs or tissues.Therefore,advancing our understanding of the inter-organ communication process is believed to provide a new perspective for treating various human diseases.展开更多
基金This work was supported by grants from the National Science and Technology Major Project of China(2016YFC1102705)the National Natural Science Foundation Projects of China(8206113022,92049201,81770873,81822012,81771043,81802193,81970898)+1 种基金the Shanghai Academic Leader of Science and Technology Innovation Action Plan(20XD1424000)the Shanghai Experimental Animal Research Project of Science and Technology Innovation Action Plan(201409006400).
文摘Deep learning(DL)is currently revolutionizing peptide drug development due to both computational advances and the substantial recent expansion of digitized biological data.However,progress in oligopeptide drug development has been limited,likely due to the lack of suitable datasets and difficulty in identifying informative features to use as inputs for DL models.Here,we utilized an unsupervised deep learning model to learn a semantic pattern based on the intrinsically disordered regions of~171 known osteogenic proteins.Subsequently,oligopeptides were generated from this semantic pattern based on Monte Carlo simulation,followed by in vivo functional characterization.A five amino acid oligopeptide(AIB5P)had strong bone-formation-promoting effects,as determined in multiple mouse models(e.g.,osteoporosis,fracture,and osseointegration of implants).Mechanistically,we showed that AIB5P promotes osteogenesis by binding to the integrinα5 subunit and thereby activating FAK signaling.In summary,we successfully established an oligopeptide discovery strategy based on a DL model and demonstrated its utility from cytological screening to animal experimental verification.
基金supported by the National Natural Science Foundation of China(no.92049201).
文摘OSTEOKINES IN INTER-ORGAN COMMUNICATIONS The concept of“organic wholeness”permeates all the fields of traditional Chinese medicine,which is also widely accepted by modern medicine.The wealth of knowledge regarding inter-organ communications generated in the latest decades provided solid evidence that human physiology and pathophysiology involve systematic interactions between multiple organs or tissues.Therefore,advancing our understanding of the inter-organ communication process is believed to provide a new perspective for treating various human diseases.