The association between miRNA and disease has attracted more and more attention.Until now,existing methods for identifying miRNA related disease mainly rely on top-ranked association model,which may not provide a full...The association between miRNA and disease has attracted more and more attention.Until now,existing methods for identifying miRNA related disease mainly rely on top-ranked association model,which may not provide a full landscape of association between miRNA and disease.Hence there is strong need of new computational method to identify the associations from miRNA group view.In this paper,we proposed a framework,MDA-TOEPGA,to identify miRNAdisease association based on two-objective evolutionary programming genetic algorithm,which identifies latent miRNAdisease associations from the view of functional module.To understand the miRNA functional module in diseases,the case study is presented.We have been compared MDA-TOEPGA with several state-of-the-art functional module algorithm.Experimental results showed that our method cannot only outperform classical algorithms,such as K-means,IK-means,MCODE,HC-PIN,and ClusterONE,but can also achieve an ideal overall performance in terms of a composite score consisting of f1,Sensitivity,and Accuracy.Altogether,our study showed that MDA-TOEPGA is a promising method to investigate miRNA-disease association from the landscapes of functional module.展开更多
Phytoene synthase （PSY） is the crucial plastidial enzyme in the carotenoid biosynthetic pathway. However, its post-translational regulation remains elusive. Likewise, Clp protease constitutes a central part of the p...Phytoene synthase （PSY） is the crucial plastidial enzyme in the carotenoid biosynthetic pathway. However, its post-translational regulation remains elusive. Likewise, Clp protease constitutes a central part of the plastid protease network, but its substrates for degradation are not well known. In this study, we report that PSY is a substrate of the Clp protease. PSY was uncovered to physically interact with various Clp protease subunits （i.e., ClpS1, CIpC1, and CIpD）. High levels of PSY and several other carotenogenic enzyme proteins overac- cumulate in the clpcl, clpp4, and clprl-2 mutants. The overaccumulated PSY was found to be partially enzy- matically active. Impairment of Clp activity in clpcl results in a reduced rate of PSY protein turnover, further supporting the role of Clp protease in degrading PSY protein. On the other hand, the ORANGE （OR） protein, a major post-translational regulator of PSY with holdase chaperone activity, enhances PSY protein stability and increases the enzymatically active proportion of PSY in clpcl, counterbalancing CIp-mediated proteol- ysis in maintaining PSY protein homeostasis. Collectively, these findings provide novel insights into the qual- ity control of plastid-localized proteins and establish a hitherto unidentified post-translational regulatory mechanism of carotenogenic enzymes in modulating carotenoid biosynthesis in plants.展开更多
基金This work was supported in part by the National Natural Science Foundation of China under Grants 61873089,62032007the Key Project of the Education Department of Hunan Province under Grant 20A087the Innovation Platform Open Fund Project of Hunan Provincial Education Department under Grant 20K025.
文摘The association between miRNA and disease has attracted more and more attention.Until now,existing methods for identifying miRNA related disease mainly rely on top-ranked association model,which may not provide a full landscape of association between miRNA and disease.Hence there is strong need of new computational method to identify the associations from miRNA group view.In this paper,we proposed a framework,MDA-TOEPGA,to identify miRNAdisease association based on two-objective evolutionary programming genetic algorithm,which identifies latent miRNAdisease associations from the view of functional module.To understand the miRNA functional module in diseases,the case study is presented.We have been compared MDA-TOEPGA with several state-of-the-art functional module algorithm.Experimental results showed that our method cannot only outperform classical algorithms,such as K-means,IK-means,MCODE,HC-PIN,and ClusterONE,but can also achieve an ideal overall performance in terms of a composite score consisting of f1,Sensitivity,and Accuracy.Altogether,our study showed that MDA-TOEPGA is a promising method to investigate miRNA-disease association from the landscapes of functional module.
文摘Phytoene synthase （PSY） is the crucial plastidial enzyme in the carotenoid biosynthetic pathway. However, its post-translational regulation remains elusive. Likewise, Clp protease constitutes a central part of the plastid protease network, but its substrates for degradation are not well known. In this study, we report that PSY is a substrate of the Clp protease. PSY was uncovered to physically interact with various Clp protease subunits （i.e., ClpS1, CIpC1, and CIpD）. High levels of PSY and several other carotenogenic enzyme proteins overac- cumulate in the clpcl, clpp4, and clprl-2 mutants. The overaccumulated PSY was found to be partially enzy- matically active. Impairment of Clp activity in clpcl results in a reduced rate of PSY protein turnover, further supporting the role of Clp protease in degrading PSY protein. On the other hand, the ORANGE （OR） protein, a major post-translational regulator of PSY with holdase chaperone activity, enhances PSY protein stability and increases the enzymatically active proportion of PSY in clpcl, counterbalancing CIp-mediated proteol- ysis in maintaining PSY protein homeostasis. Collectively, these findings provide novel insights into the qual- ity control of plastid-localized proteins and establish a hitherto unidentified post-translational regulatory mechanism of carotenogenic enzymes in modulating carotenoid biosynthesis in plants.
