The Research Of The Apoptosis And Autophagy Bi-functional Proteins By Clustering Algorithm

Autophagy and apoptosis,as two main forms of programmed cell death,constitute distinct cell processes and often lead to completely opposite cell fates.In recent years,biological researchers have found gradually that there is a complex interaction and connection between the two,and this interaction affects the function of autophagy and apoptosis,which is critical to the fate of cells.However,due to the large number and types of proteins involved in autophagy and apoptosis,it is difficult to carry out a comprehensive analysis with the current traditional biological experimental methods.Moreover,the labeling of protein autophagy and apoptosis biological function crossing in the existing database is obviously limited to the current limited literature reports and experimental results,providing incomplete information.Therefore,it is still unclear that which bifunctional proteins are responsible for the interaction between autophagy and apoptosis,and how large these bifunctional proteins should be.This situation makes the mechanism and influence of the interaction between autophagy and apoptosis unable to be explained in detail and fully understood,and even some contradictions and controversies arise.In recent five years,the field of bioinformatics has begun to use topological clustering algorithm to find multifunctional proteins from PPI(protein-protein interaction)network.The advantage of this method is that it does not completely rely on the protein function information suggested in the existing literature or experiments,but also considers the complex network relationship between proteins on the basis of information collection,and then uses the protein relationship to reasonably speculate the function of proteins to find multifunctional proteins.Therefore,PPI protein network topological clustering algorithm is very suitable for solving the problem of searching for autophagy and apoptosis bifunctional proteins.Among them,OCG clustering algorithm uses an extension of Newman's modularity function into the hierarchical structure to obtain overlapping clustering.It is one of the most commonly used and fastest developing overlapping clustering algorithm for PPI network image processing at present.Through this method,a series of special multifunctional proteins have been successfully obtained and proved to be at the intersection of topological clustering,with more central positions in the network and more functional domains.Therefore,OCG clustering algorithm was selected in this study to search for autophagy and apoptosis bifunctional proteins.This study constructed a large human autophagy and apoptosis related PPI network which contains 2616 proteins,35800 PPIs.Then we construct a network analysis process based on this PPI network and OCG topology clustering method.In this way,this study break through the limited protein function experiment information from the existing literatures or databases.We use protein interaction relationship combine with the protein interaction relationships to undergoing reasonable prediction of protein function.Through this method,this research explore the relationship between autophagy and apoptosis in all human proteome data level for the first time,and we got a predicted bifunctional protein sets contains 151 autophagy and apoptosis bifunctional proteins for the first time.In this way we show a whole human autophagy and apoptosis bifunctional protein group from a new and global view.This study found that autophagy and apoptosis bifunctional proteins have more interactions between protein and contain more functional domains,subordinate to more OCG topological clusters compared to other proteins in the network,and it has a more central position and higher connectedness of the protein in the conditions that depending fewer PPIs than hubs sets in the network.All of these characteristics are in line with the prevailing multifunctional protein research conclusion.In conclusion,the calculated autophagy and apoptosis bifunctional proteome shows some particularity in the protein network.They are of relatively high research value in the global protein signal transduction network related to cell death rather than being limited to a certain field of autophagy or apoptosis.In the prediction set of this study,in addition to 56 bifunctional proteins involved in autophagy and apoptosis that have been reported in a large number of literatures,there are 94 new bifunctional proteins that have not been reported.Among these new bifunctional proteins,this study provides experimental clues and scientific research prospects of 8 proteins and their new functions that have not been widely concerned in the field of autophagy and apoptosis,including PAK2,HRAS,RL40,ELOC,RBX1,CTNB1,PLCG1 and RAD5.These findings provide directions and clues for the study of system biology such as proteomics.Based on these findings,more new protein-protein interactions will be discovered and more structural information and biological functions of proteins will be studied.