Layered and annotation grouped interactome demonstrates enhanced autophagy activity in a recurrent experimental autoimmune uveitis T cell line

【作者】 贾秀志； 任欢；

【机构】 哈尔滨医科大学；

【摘要】 Background:Autoimmune uveitis is usually a recurrent-remitting disease and seldom monophasic.However, the mechanism is not well understood.Methods:Publicly available gene expression data of recurrent and monophasic T cell lines were linked with the Fun Coup(functional coupling between proteins) database to construct a global interactome.Cytoscape and the Cerebral(Cell Region-Based Rendering And Layout) plugin were then used to establish layered interactome based upon information of subcellular protein localizations that was retrieved from the Human Protein Reference Database(HP RD).After the layered interactomes were individually annotated according to gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes database(KEGG), the Clue GO plugin was applied to group these functional annotations in order to decipher cellular events at the organelle level in the 3 different layers.Results:The global functional protein interactome was constructed and divided into 3 layers:the plasma membrane, the cytoplasm, and the nucleus.Clue GO analysis showed that 9 groups of annotations were obtained characterizing over-represented biological processes in the 3 different layers.Of the 5 groups annotated in the cytoplasm layer, "autophagosome formation"(correlated, p=0.025) was directly annotated, the otherannotated processes also showed clear association with autophagy.Moreover, the grouped annotations in the plasma membrane and the nucleus signified active processes that highly linked with T cell activation and autoimmunity.Conclusions:This study shows that layered and annotation grouped analysis provides great insights, especially at the organelle level, into the mechanism of recurrent uveitis.The recurrent T cell line showed increased autophagy activity.更多还原

【Abstract】 Background:Autoimmune uveitis is usually a recurrent-remitting disease and seldom monophasic.However, the mechanism is not well understood.Methods:Publicly available gene expression data of recurrent and monophasic T cell lines were linked with the Fun Coup(functional coupling between proteins) database to construct a global interactome.Cytoscape and the Cerebral(Cell Region-Based Rendering And Layout) plugin were then used to establish layered interactome based upon information of subcellular protein localizations that was retrieved from the Human Protein Reference Database(HP RD).After the layered interactomes were individually annotated according to gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes database(KEGG), the Clue GO plugin was applied to group these functional annotations in order to decipher cellular events at the organelle level in the 3 different layers.Results:The global functional protein interactome was constructed and divided into 3 layers:the plasma membrane, the cytoplasm, and the nucleus.Clue GO analysis showed that 9 groups of annotations were obtained characterizing over-represented biological processes in the 3 different layers.Of the 5 groups annotated in the cytoplasm layer, "autophagosome formation"(correlated, p=0.025) was directly annotated, the otherannotated processes also showed clear association with autophagy.Moreover, the grouped annotations in the plasma membrane and the nucleus signified active processes that highly linked with T cell activation and autoimmunity.Conclusions:This study shows that layered and annotation grouped analysis provides great insights, especially at the organelle level, into the mechanism of recurrent uveitis.The recurrent T cell line showed increased autophagy activity.更多还原