Exploring Clinical Diagnosis Biomarkers For Patients With Schizophrenia Based On Isotope Coded Derivatization Technology

Schizophrenia is a group of severe mental illnesses.At present,the primary diagnosis method is to rely on medical history and mental state.The lack of characteristic biomarkers can easily lead to misdiagnosis.Therefore,there is an urgent need to find biomarkers that can be used to assist diagnosis.Recently,non-targeted metabolomics based on LC-MS is a powerful means for discovering biomarkers,but it is limited by the sensitivity and identification of metabolites.Therefore,isotope-coded derivatization combined with metabolomics technology is used to improve the detectability of metabolites and develop data post-processing methods to simplify the identification process of metabolites.This project used isotope O-phthalaldehyde(OPA)reagents and Ophthalaldehyde-D4(OPA-D4)reagents to code human serum samples with isotope derivatization.Using the difference in mass defect between OPA and OPA-D4,a narrow-range mass defect filtering data post-processing technology(NMDF)was developed to simplify non-targeted data sets,so as to identify endogenous primary amine metabolites quickly and accurately.Through non-targeted semi-quantitative analysis of serum samples of schizophrenia patients and healthy people,the primary amine metabolites with significant differences were found and their metabolic pathways were analyzed.Primary amine metabolites with significant difference and their pathway-related metabolites were quantitatively analysis.Then,statistical analysis methods were used to find potential biomarkers for the clinical diagnosis of schizophrenia.260 possible endogenous primary amine compounds were found through NMDF,and 195 of them were recognized and identified.OPLS-DA analysis of non-targeted semi-quantitative data(VIP>1,|Pcorr|>0.58)found two significantly different metabolites,2-Aminoacrylic acid and DL-Homocysteine.DL-Homocysteine and 13 related metabolites of its metabolic pathways were quantitatively analyzed.Finally,four potential biomarkers were found by t-test or Mann-Whitney test(p<0.05):DLHomocysteine,S-Adenosyl-L-methionine,spermidine and N,N-Dimethylglycine.The results show that the research ideas adopted in this study are feasible for the discovery of disease biomarkers,especially the NMDF data processing technology,which has a lot of reference in simplifying the process of complex data sets.