scholarly journals Investigation of multiple sclerosis-related pathways through the integration of genomic and proteomic data

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11922
Author(s):  
Elif Everest ◽  
Ege Ülgen ◽  
Ugur Uygunoglu ◽  
Melih Tutuncu ◽  
Sabahattin Saip ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
False Negative ◽  
Proteome Analysis ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Coagulation Cascade ◽  
Differentially Expressed Proteins ◽  
Proteomic Data ◽  
Genome Wide ◽  
Immunological Mechanisms

Background Multiple sclerosis (MS) has a complex pathophysiology, variable clinical presentation, and unpredictable prognosis; understanding the underlying mechanisms requires combinatorial approaches that warrant the integration of diverse molecular omics data. Methods Here, we combined genomic and proteomic data of the same individuals among a Turkish MS patient group to search for biologically important networks. We previously identified differentially-expressed proteins by cerebrospinal fluid proteome analysis of 179 MS patients and 42 non-MS controls. Among this study group, 11 unrelated MS patients and 60 independent, healthy controls were subjected to whole-genome SNP genotyping, and genome-wide associations were assessed. Pathway enrichment analyses of MS-associated SNPs and differentially-expressed proteins were conducted using the functional enrichment tool, PANOGA. Results Nine shared pathways were detected between the genomic and proteomic datasets after merging and clustering the enriched pathways. Complement and coagulation cascade was the most significantly associated pathway (hsa04610, P = 6.96 × 10−30). Other pathways involved in neurological or immunological mechanisms included adherens junctions (hsa04520, P = 6.64 × 10−25), pathogenic Escherichia coli infection (hsa05130, P = 9.03 × 10−14), prion diseases (hsa05020, P = 5.13 × 10−13). Conclusion We conclude that integrating multiple datasets of the same patients helps reducing false negative and positive results of genome-wide SNP associations and highlights the most prominent cellular players among the complex pathophysiological mechanisms.

scholarly journals Metformin as a Potential Agent in the Treatment of Multiple Sclerosis

2020 ◽  
Vol 21 (17) ◽  
pp. 5957
Author(s):  
Angela Dziedzic ◽  
Joanna Saluk-Bijak ◽  
Elzbieta Miller ◽  
Michal Bijak
Keyword(s):  
Multiple Sclerosis ◽  
Inflammatory Diseases ◽  
Coagulation Cascade ◽  
Oral Antidiabetic Agent ◽  
Immunological Mechanisms ◽  
Increased Risk ◽  
The Central Nervous System ◽  
Synthetic Derivative ◽  
Ischemic Events ◽  
Ms Therapy

Metformin, a synthetic derivative of guanidine, is commonly used as an oral antidiabetic agent and is considered a multi-vector application agent in the treatment of other inflammatory diseases. Recent studies have confirmed the beneficial effect of metformin on immune cells, with special emphasis on immunological mechanisms. Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) characterized by various clinical courses. Although the pathophysiology of MS remains unknown, it is most likely a combination of disturbances of the immune system and biochemical pathways with a disruption of blood–brain barrier (BBB), and it is strictly related to injury of intracerebral blood vessels. Metformin has properties which are greatly desirable for MS therapy, including antioxidant, anti-inflammatory or antiplatelet functions. The latest reports relating to the cardiovascular disease confirm an increased risk of ischemic events in MS patients, which are directly associated with a coagulation cascade and an elevated pro-thrombotic platelet function. Hence, this review examines the potential favourable effects of metformin in the course of MS, its role in preventing inflammation and endothelial dysfunction, as well as its potential antiplatelet role.

scholarly journals iTRAQ-Based Proteomics of Chronic Renal Failure Rats after FuShengong Decoction Treatment Reveals Haptoglobin and Alpha-1-Antitrypsin as Potential Biomarkers

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Yu Yang ◽  
Junmeng Wei ◽  
Xuekuan Huang ◽  
Mingjun Wu ◽  
Zhenbing Lv ◽  
...  
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Differentially Expressed ◽  
Coagulation Cascade ◽  
Control Group ◽  
Differentially Expressed Proteins ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Alpha 1 Antitrypsin ◽  
Global Health Problem

Background. Chronic renal failure (CRF) has become a global health problem and bears a huge economic burden. FuShengong Decoction (FSGD) as traditional Chinese medicine has multiple pharmacological effects. Objectives. To understand the underlying molecular mechanism and signaling pathway involved in the FSGD treatment of CRF and screen differentially expressed proteins in rats with CRF treated with FSGD. Methods. Thirty-three male Sprague-Dawley rats were randomly divided into control group, CRF group, and FSGD group. Differentially expressed proteins were screened by iTRAQ coupled with nanoLC-MS/MS, and these identified proteins were later analyzed by GO, KEGG, and STRING. Additionally, haptoglobin (HP) and alpha-1-antitrypsin (AAT) were finally verified by ELISA, Western blot, and real time PCR. Results. A total of 417 proteins were identified. Nineteen differentially expressed proteins were identified in the FSGD group compared with the model group, of which 3 proteins were upregulated and 16 proteins were downregulated. Cluster analysis indicated that inflammatory response was associated with these proteins and complement and coagulation cascade pathways were predominantly involved. The validation methods further confirmed that the levels of HP and AAT were significantly increased. Conclusions. HP and AAT may be the important biomarkers in the pathogenesis of CRF and FSGD therapy.

scholarly journals Bayesian identification of protein differential expression in multi-group isobaric labelled mass spectrometry data

2014 ◽  
Vol 13 (5) ◽  
Author(s):  
Howsun Jow ◽  
Richard J. Boys ◽  
Darren J. Wilkinson
Keyword(s):  
Mass Spectrometry ◽  
Simulated Data ◽  
Differentially Expressed ◽  
Mass Spectrometry Data ◽  
Control Group ◽  
Differentially Expressed Proteins ◽  
Statistical Methodology ◽  
Proteomic Data ◽  
Bayesian Identification ◽  
Multiple Groups

AbstractIn this paper we develop a Bayesian statistical inference approach to the unified analysis of isobaric labelled MS/MS proteomic data across multiple experiments. An explicit probabilistic model of the log-intensity of the isobaric labels’ reporter ions across multiple pre-defined groups and experiments is developed. This is then used to develop a full Bayesian statistical methodology for the identification of differentially expressed proteins, with respect to a control group, across multiple groups and experiments. This methodology is implemented and then evaluated on simulated data and on two model experimental datasets (for which the differentially expressed proteins are known) that use a TMT labelling protocol.

Proteins with potential role in analgesic effect of spinal cord stimulation on neuropathic pain

2014 ◽  
Vol 5 (3) ◽  
pp. 209-210
Author(s):  
A. Lind ◽  
P. Emami ◽  
M. Sjödin ◽  
L. Katila ◽  
M. Wetterhall ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Network Analysis ◽  
Spinal Cord Stimulation ◽  
Analgesic Effect ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Differentially Expressed Proteins ◽  
Label Free ◽  
Ionization Source

AbstractAimsWe aimed to find proteins of relevance to the prolonged analgesic effect of spinal cord stimulation (SCS) for patients with neuropathic pain.MethodsThe proteomes of cerebrospinal fluid (CSF) from 14 neuropathic pain patients using spinal cord stimulation (SCS) was compared to the CSF proteomes of the same patients when not using the stimulator. Samples were analyzed by dimethyl label and label free shotgun proteomics approach. Samples were prepared by immunoaffinity fractionation and then separated by reversed phase nanoliquid chromatography coupled to an electrospray ionization source and analyzed by high resolution tandem mass spectrometry. The proteins were comparatively quantified on the peptide level and ranked based on numbers of regulated peptides. Then the dimethyl and label free analysis results were combined. In order to group proteins by function and interactions, a functional enrichment network analysis was performed using the String (Search Tool for the Retrieval of Interacting Genes/Proteins) database on all significantly differentially expressed proteins.ResultsWe found 87 differentially expressed proteins. Network analysis showed a high level of enrichment in interactions between the proteins involved in platelet degranulation and wound healing with p-values 2.48E−11 and 4.58E−08. We also recognized two additional clusters related to complement and coagulation cascades and neuropeptides. None of these proteins have been implicated in SCS mechanism previously.ConclusionsUp- and down-regulations of immunological proteins and neuropeptides may explain the prolonged relief of neuropathic pain obtained after SCS. These findings contribute a new basis for understanding of SCS analgesic mechanism in human neuropathic pain. Further verification studies of these initial findings are needed.

Proteome analysis of virulent Aeromonas hydrophila reveals the upregulation of iron acquisition systems in the presence of a xenosiderophore

2020 ◽  
Vol 367 (20) ◽  
Author(s):  
Miles D Lange ◽  
Jason Abernathy ◽  
Craig A Shoemaker ◽  
Dunhua Zhang ◽  
Augustus Kirby ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Ictalurus Punctatus ◽  
Aeromonas Hydrophila ◽  
Iron Acquisition ◽  
Chelating Agent ◽  
Proteome Analysis ◽  
Differentially Expressed ◽  
Differentially Expressed Proteins ◽  
Protein Protein Interactions ◽  
Virulent Aeromonas Hydrophila

ABSTRACT The Gram-negative bacterium, Aeromonas hydrophila, has been responsible for extensive losses in the catfish industry for over a decade. Due to this impact, there are ongoing efforts to understand the basic mechanisms that contribute to virulent A. hydrophila (vAh) outbreaks. Recent challenge models demonstrated that vAh cultured in the presence of the iron chelating agent deferoxamine mesylate (DFO) were more virulent to channel catfish (Ictalurus punctatus). Interestingly, differential gene expression of select iron acquisition genes was unremarkable between DFO and non-DFO cultures, posing the question: why the increased virulence? The current work sought to evaluate growth characteristics and protein expression of vAh after the addition of DFO. A comparative proteome analysis revealed differentially expressed proteins among tryptic soy broth (TSB) and TSB + DFO treatments. Upregulated proteins identified among the TSB + DFO treatment were enriched for gene ontology groups including iron ion transport, siderophore transport and siderophore uptake transport, all iron acquisition pathways. Protein-protein interactions were also evaluated among the differentially expressed proteins and predicted that many of the upregulated iron acquisition proteins likely form functional physiological networks. The proteome analysis of the vAh reveals valuable information about the basic biological processes likely leading to increased virulence during iron restriction in this organism.

scholarly journals Genome-wide meta-analysis reveals shared new loci in systemic seropositive rheumatic diseases

2018 ◽  
Vol 78 (3) ◽  
pp. 311-319 ◽  
Author(s):  
Marialbert Acosta-Herrera ◽  
Martin Kerick ◽  
David González-Serna ◽  
Cisca Wijmenga ◽  
Andre Franke ◽  
...  
Keyword(s):  
Rheumatic Diseases ◽  
Lupus Erythematosus ◽  
Clinical Symptoms ◽  
Drug Repositioning ◽  
Familial Aggregation ◽  
Meta Analysis ◽  
Functional Enrichment ◽  
Coagulation Cascade ◽  
Potential Candidate ◽  
Genome Wide

ObjectiveImmune-mediated inflammatory diseases (IMIDs) are heterogeneous and complex conditions with overlapping clinical symptoms and elevated familial aggregation, which suggests the existence of a shared genetic component. In order to identify this genetic background in a systematic fashion, we performed the first cross-disease genome-wide meta-analysis in systemic seropositive rheumatic diseases, namely, systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis and idiopathic inflammatory myopathies.MethodsWe meta-analysed ~6.5 million single nucleotide polymorphisms in 11 678 cases and 19 704 non-affected controls of European descent populations. The functional roles of the associated variants were interrogated using publicly available databases.ResultsOur analysis revealed five shared genome-wide significant independent loci that had not been previously associated with these diseases: NAB1, KPNA4-ARL14, DGQK, LIMK1 and PRR12. All of these loci are related with immune processes such as interferon and epidermal growth factor signalling, response to methotrexate, cytoskeleton dynamics and coagulation cascade. Remarkably, several of the associated loci are known key players in autoimmunity, which supports the validity of our results. All the associated variants showed significant functional enrichment in DNase hypersensitivity sites, chromatin states and histone marks in relevant immune cells, including shared expression quantitative trait loci. Additionally, our results were significantly enriched in drugs that are being tested for the treatment of the diseases under study.ConclusionsWe have identified shared new risk loci with functional value across diseases and pinpoint new potential candidate loci that could be further investigated. Our results highlight the potential of drug repositioning among related systemic seropositive rheumatic IMIDs.

scholarly journals Differential Proteome Analysis of Hybrid Bamboo (Bambusa pervariabilis × Dendrocalamopsis grandis) Under Fungal Stress (Arthrinium phaeospermum)

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Shujiang Li ◽  
Xinmei Fang ◽  
Shan Han ◽  
Tianhui Zhu ◽  
Hanmingyue Zhu
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Quantitative Analysis ◽  
Proteome Analysis ◽  
Enrichment Analysis ◽  
Pathogenic Fungi ◽  
Differentially Expressed ◽  
Differentially Expressed Proteins ◽  
Differential Proteins ◽  
Arthrinium Phaeospermum

AbstractIn this study, TMT (tandem mass tag)-labeled quantitative protein technology combined with LC–MS/MS (liquid chromatography-mass spectrometry/mass spectrometry) was used to isolate and identify the proteins of the hybrid bamboo (Bambusa pervariabilis × Dendrocalamopsis grandis) and the bamboo inoculated with the pathogenic fungi Arthrinium phaeospermum. A total of 3320 unique peptide fragments were identified after inoculation with either A. phaeospermum or sterile water, and 1791 proteins were quantified. A total of 102 differentially expressed proteins were obtained, of which 66 differential proteins were upregulated and 36 downregulated in the treatment group. Annotation and enrichment analysis of these peptides and proteins using the GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) databases with bioinformatics software showed that the differentially expressed protein functional annotation items were mainly concentrated on biological processes and cell components. The LC–PRM/MS (liquid chromatography-parallel reaction monitoring/mass spectrometry) quantitative analysis technique was used to quantitatively analyze 11 differential candidate proteins obtained by TMT combined with LC–MS/MS. The up–down trend of 10 differential proteins in the PRM results was consistent with that of the TMT quantitative analysis. The coincidence rate of the two results was 91%, which confirmed the reliability of the proteomic results. Therefore, the differentially expressed proteins and signaling pathways discovered here may be the further concern for the bamboo-pathogen interaction studies.

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