Dataset Information

Schizophrenia Proteome Research

ABSTRACT: Despite of multiple systematic studies of schizophrenia pathogenesis, reconstruction of the mechanism established on proteomics, metabolomics, and genome-wide significant loci is still a challenging task. We suggested that advanced data for quantitative proteomics, metabolomics, and genome-wide association study (GWAS) may enhance the current evidence and fundamental knowledge about molecular pathogenesis of schizophrenia. Liquide chromatography and ultra-high-resolution mass-spectrometry were utilized for proteomic and metabolomic assay, and high throughput genotyping for the GWAS study. Proteomic and metabolomic results were quantitatively evaluated and overlayed on the GWAS data. After statistical analysis using R-package, the resulting features were associated in a multilayer mode with adjusted biological processes in a reconstructed unified map of molecular events. We have identified 20 DFE proteins that were validated on an independent cohort of patients that are significant for schizophrenia, including ALS, A1AG1, PEDF, VTDB, CERU, APOB, APOH, FASN, GPX3, etc. Almost half of them are new for schizophrenia. The metabolomic survey revealed 18 compounds most of which were the part transformation of tyrosine and steroids with the incline to androgens (androsterone sulfate, thyroliberin, thyroxine, dihydrotestosterone, androstenedione, cholesterol sulfate, metanephrine, dopaquinone, etc.) which were extracted as group-specific determinants that permits to isolate patients with schizophrenia. The GWAS assay revealed 52 loci were integrated into proteome-metabolome data as significantly implicated in schizophrenia. We integrated three layers of omics science (proteomics, metabolomics and GWAS) and quantitative analysis utilized systematic approach to reconstruct the proposed map of molecular events associated with the considered psychopathology. The resulting interplay between different layers emphasized strict implication of lipids metabolism, oxidative stress, imbalance in steroidogenesis and associated impartments of thyroid hormones and sex hormones interconnection. The proposed interplay map can give opportunity in the understanding how the regulation of distinct metabolic axis is achieved and what happens in proteome arrangements to produce a schizophrenia-specific pattern of pathology condition.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma

DISEASE(S): Schizophrenia

SUBMITTER: Arthur Kopylov

LAB HEAD: Dr. Anna L. Kaysheva

PROVIDER: PXD035863 | Pride | 2023-02-08

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	CNT_20190613_01_YGW735.mgf	Mgf
	CNT_20190613_01_YGW735.mzid.gz	Mzid
	CNT_20190613_01_YGW735.omx	Other
	CNT_20190613_01_YGW735.raw	Raw
	CNT_20190613_02_KOHYW0.mgf	Mgf

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Publications

Consolidation of metabolomic, proteomic, and GWAS data in connective model of schizophrenia.

Kopylov Arthur T AT Stepanov Alexander A AA Butkova Tatiana V TV Malsagova Kristina A KA Zakharova Natalia V NV Kostyuk Georgy P GP Elmuratov Artem U AU Kaysheva Anna L AL

Scientific reports 20230206 1

Despite of multiple systematic studies of schizophrenia based on proteomics, metabolomics, and genome-wide significant loci, reconstruction of underlying mechanism is still a challenging task. Combination of the advanced data for quantitative proteomics, metabolomics, and genome-wide association study (GWAS) can enhance the current fundamental knowledge about molecular pathogenesis of schizophrenia. In this study, we utilized quantitative proteomic and metabolomic assay, and high throughput geno ...[more]

PMID: 36747015

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