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Proteomics and bioinformatics approaches for the identification of plasma biomarkers to detect Parkinson's disease.

Wenwen Dong | Chang Qiu | Dawei Gong | Xu Jiang | Wan Liu | Weiguo Liu | Li Zhang | Wenbin Zhang
Experimental and therapeutic medicine | 2019

The aim of the present study was to screen for biomarkers of Parkinson's disease (PD) using proteomics and bioinformatics approaches. PD patients were divided into three groups: Those without surgery (PD1 group); those who had undergone deep brain stimulation (DBS) surgery without electrode stimulation (PD2 group); and those who had undergone DBS surgery with 1 month of electrode stimulation (PD3 group). The non-Parkinson control group (CK group) was also involved. Quantitative proteomic analysis of human sera was performed through the use of tandem mass tag markers and liquid chromatography-mass spectrometry (LC-MS)-based techniques. For the proteins with quantitative information, a systematic bioinformatics analysis was then performed, including protein annotation, functional classification, functional enrichment and cluster analysis based on functional enrichment. Of the 739 proteins identified, quantitative information was available for 644. With regard to differential expression, 18 upregulated and 21 downregulated proteins were screened in the PD1/CK comparison group; 12 upregulated and 12 downregulated proteins in the PD2/PD1 comparison group; and 16 upregulated and 19 downregulated proteins in the PD3/PD2 comparison group. Coiled-coil domain-containing protein 154 (CCDC154) and tripartite motif-containing protein 3 (TRIM3) were key proteins involved in the molecular mechanisms of PD, participating in intracellular vesicle, ubiquitin protein ligase and transition metal ion-binding activities. After DBS surgery, desert hedgehog protein (DHH) was downregulated, whereas neuropilin-2 (NRP2) was upregulated; these participated in the ensheathment of neurons and the semaphorin receptor complex, respectively. The expression level of chloride intracellular channel protein 1 (CLIC1) was increased after 1 month of electrode stimulation following DBS. By combining proteomic approaches and LC-MS methods, significant proteins including CCDC154, TRIM3, DHH, NRP2 and CLIC1 were detected with high specificity and sensitivity. These may be used as novel biomarkers for early diagnosis of PD and the future development of treatments.

Pubmed ID: 31572530

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Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.


InterPro (tool)

RRID:SCR_006695

Service providing functional analysis of proteins by classifying them into families and predicting domains and important sites. They combine protein signatures from a number of member databases into a single searchable resource, capitalizing on their individual strengths to produce a powerful integrated database and diagnostic tool. This integrated database of predictive protein signatures is used for the classification and automatic annotation of proteins and genomes. InterPro classifies sequences at superfamily, family and subfamily levels, predicting the occurrence of functional domains, repeats and important sites. InterPro adds in-depth annotation, including GO terms, to the protein signatures. You can access the data programmatically, via Web Services. The member databases use a number of approaches: # ProDom: provider of sequence-clusters built from UniProtKB using PSI-BLAST. # PROSITE patterns: provider of simple regular expressions. # PROSITE and HAMAP profiles: provide sequence matrices. # PRINTS provider of fingerprints, which are groups of aligned, un-weighted Position Specific Sequence Matrices (PSSMs). # PANTHER, PIRSF, Pfam, SMART, TIGRFAMs, Gene3D and SUPERFAMILY: are providers of hidden Markov models (HMMs). Your contributions are welcome. You are encouraged to use the ''''Add your annotation'''' button on InterPro entry pages to suggest updated or improved annotation for individual InterPro entries.

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Thermo Fisher Scientific (tool)

RRID:SCR_008452

Commercial vendor and service provider of laboratory reagents and antibodies. Supplier of scientific instrumentation, reagents and consumables, and software services.

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KEGG (tool)

RRID:SCR_012773

Integrated database resource consisting of 16 main databases, broadly categorized into systems information, genomic information, and chemical information. In particular, gene catalogs in completely sequenced genomes are linked to higher-level systemic functions of cell, organism, and ecosystem. Analysis tools are also available. KEGG may be used as reference knowledge base for biological interpretation of large-scale datasets generated by sequencing and other high-throughput experimental technologies.

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MaxQuant (tool)

RRID:SCR_014485

A quantitative proteomics software package for analyzing large-scale mass-spectrometric data sets. It is a set of algorithms that include peak detection and scoring of peptides, mass calibration, database searches for protein identification, protein quantification, and provides summary statistics.

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