Protein Disulfide Isomerase A2 (PDIA2) Computational Network And Systems Analysis In Human Left Brain Cognition

In this paper,we constructed a molecular and knowledge network of feedback/upstream/downstream activation and inhibition of protein disulfide isomerase A2（PDIA2）in human left brain,which is closely related to cognition.By integrating Gene（protein）reconstruction network reasoning algorithm（GRNInfer）and Annotate,visualize and integrate discovery databases（DAVID）,based on the common knowledge of different molecules of feedback/upstream/downstream activation and inhibition of PDIA2,we proposed and verified a new hypothesis that PDIA2 regulates human left brain cognition:Integrating PDIA2 feedback-inhibition,downstream-inhibition Alzheimer’s disease,the corresponding feed-inhibition protein domain specific binding,platelet activation,neurotrophin TRK receptor signaling pathway,membrane organization,Rap1 signaling pathway,Insulin signaling pathway,G protein signaling | stimulatory C type lectin receptor signaling pathway,Fc epsilon receptor signaling pathway,Oocyte meiosis | nitric oxide synthase regulator activity,positive regulation of protein serine/threonine kinase activity,Estrogen signaling pathway | thioesterase binding,Ras signaling pathway | small molecule metabolic process | cGMP PKG signaling pathway | structural constituent of cytoskeleton | apoptosis | cytosol in SERINC3,NR1D2 2,HSP90AB1,PRKCI₂,R37702,GTF2I₁ subnetwork;or downstream-inhibition blood coagulation,metabolic process | Gastric acid secretion,second messenger mediated signaling | post embryonic development | protein stabilization in KIF3A,U00928,GNAQ,WDR68,EID1,NDUFA5 subnetwork.PDIA2 positive self feedback inhibition Alzheimer’s disease affects cognition through platelet activation,Oocyte meiosis,protein serine/threonine kinase activity,thioesterase binding,blood coagulation,post embryonic development,Rap1 signaling pathway DNA repair for positive verification.PDIA2 positive feedback activated small GTPase mediated signal transduction,transcription initiation from RNA polymerase Ⅱ promoter,small molecule metabolic process for negative varification.Mutually verification with upstream activation and upstream inhibition,feedback and downstream inhibition cell cycle.Through the negative self feedback activation or inhibition network of PDIA2,we propose that PDIA2 speed limiting neurotrophin TRK receptor signaling pathway,negative regulation of transcription DNA templated,positive regulation of transcription DNA templated,regulation of transcription DNA templated,response to DNA damage stimulus,negative regulation of transcription from RNA polymerase Ⅱpromoter,enzyme binding,protein domain specific binding,apoptotic process,negative regulation of apoptotic process,protein stabilization,response to endogenous stimulus for negative verification.In conclusion,the above new hypothesis is put forward and verified.The new systematic analysis of PDIA2 adds theoretical and applied research on human left hemisphere cognition,and provides important theoretical basis and application value for the study of human left hemisphere cognitive mechanisms.