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A new bioinformatic insight into the associated proteins in psychiatric disorders.

ABSTRACT: BACKGROUND:Psychiatric diseases severely affect the quality of patients' lives and bring huge economic pressure to their families. Also, the great phenotypic variability among these patients makes it difficult to investigate the pathogenesis. Nowadays, bioinformatics is hopeful to be used as an effective tool for the diagnosis of psychiatric disorders, which can identify sensitive biomarkers and explore associated signaling pathways. METHODS:In this study, we performed an integrated bioinformatic analysis on 1945 mental-associated proteins including 91 secreted proteins and 593 membrane proteins, which were screened from the Universal Protein Resource (Uniport) database. Then the function and pathway enrichment analyses, ontological classification, and constructed PPI network were executed. RESULTS:Our present study revealed that the majority of mental proteins were closely related to metabolic processes and cellular processes. We also identified some significant molecular biomarkers in the progression of mental disorders, such as HRAS, ALS2, SLC6A1, SLC39A12, SIL1, IDUA, NEPH2 and XPO1. Furthermore, it was found that hub proteins, such as COMT, POMC, NPS and BDNF, might be the potential targets for mental disorders therapy. Finally, we demonstrated that psychiatric disorders may share the same signaling pathways with cancers, involving ESR1, BCL2 and MAPK3. CONCLUSION:Our data are expected to contribute to explaining the possible mechanisms of psychiatric diseases and providing a useful reference for the diagnosis and therapy of them.

SUBMITTER: Zhao W

PROVIDER: S-EPMC5108746 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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A new bioinformatic insight into the associated proteins in psychiatric disorders.

Zhao Wenlong W Yang Wenjing W Zheng Shuanglin S Hu Qiong Q Qiu Ping P Huang Xinghua X Hong Xiaoqian X Lan Fenghua F

SpringerPlus 20161114 1

<h4>Background</h4>Psychiatric diseases severely affect the quality of patients' lives and bring huge economic pressure to their families. Also, the great phenotypic variability among these patients makes it difficult to investigate the pathogenesis. Nowadays, bioinformatics is hopeful to be used as an effective tool for the diagnosis of psychiatric disorders, which can identify sensitive biomarkers and explore associated signaling pathways.<h4>Methods</h4>In this study, we performed an integrat ...[more]

PMID: 27917343

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Project description:Over the past decade, large-scale genetic studies have successfully identified hundreds of genetic variants robustly associated with risk for psychiatric disorders. However, mechanistic insight and clinical translation continue to lag the pace of risk variant identification, hindered by the sheer number of targets and their predominant noncoding localization, as well as pervasive pleiotropy and incomplete penetrance. Successful next steps require identification of "causal" genetic variants and their proximal biological consequences; placing variants within biologically defined functional contexts, reflecting specific molecular pathways, cell types, circuits, and developmental windows; and characterizing the downstream, convergent neurobiological impact of polygenicity within an individual. Here, we discuss opportunities and challenges of high-throughput transcriptomic profiling in the human brain, and how transcriptomic approaches can help pinpoint mechanisms underlying genetic risk for psychiatric disorders at a scale necessary to tackle daunting levels of polygenicity. These include transcriptome-wide association studies for risk gene prioritization through integration of genome-wide association studies with expression quantitative trait loci. We outline transcriptomic results that inform our understanding of the brain-level molecular pathology of psychiatric disorders, including autism spectrum disorder, bipolar disorder, major depressive disorder, and schizophrenia. Finally, we discuss systems-level approaches for integration of distinct genetic, genomic, and phenotypic levels, including combining spatially resolved gene expression and human neuroimaging maps. Results highlight the importance of understanding gene expression (dys)regulation across human brain development as a major contributor to psychiatric disease pathogenesis, from common variants acting as expression quantitative trait loci to rare variants enriched for gene expression regulatory pathways.

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A new bioinformatic insight into the associated proteins in psychiatric disorders.

Publications

A new bioinformatic insight into the associated proteins in psychiatric disorders.

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