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1.
Foodomics for human health: current status and perspectives.
Braconi, D, Bernardini, G, Millucci, L, Santucci, A
Expert review of proteomics. 2018;(2):153-164
Abstract
In the post-genomic era, the opportunity to combine and integrate cutting-edge analytical platforms and data processing systems allowed the birth of foodomics, 'a discipline that studies the Food and Nutrition domains through the application of advanced omics technologies to improve consumer's well-being, health, and confidence'. Since then, this discipline has rapidly evolved and researchers are now facing the daunting tasks to meet consumers' needs in terms of food traceability, sustainability, quality, safety and integrity. Most importantly, today it is imperative to provide solid evidence of the mechanisms through which food can promote human health and well-being. Areas covered: In this review, the complex relationships connecting food, nutrition and human health will be discussed, with emphasis on the relapses for the development of functional foods and nutraceuticals, personalized nutrition approaches, and the study of the interplay among gut microbiota, diet and health/diseases. Expert commentary: Evidence has been provided supporting the role of various omic platforms in studying the health-promoting effects of food and customized dietary interventions. However, although associated to major analytical challenges, only the proper integration of multi-omics studies and the implementation of bioinformatics tools and databases will help translate findings from clinical practice into effective personalized treatment strategies.
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2.
Prediction of citrullination sites by incorporating k-spaced amino acid pairs into Chou's general pseudo amino acid composition.
Ju, Z, Wang, SY
Gene. 2018;:78-83
Abstract
As one of the most important and common protein post-translational modifications, citrullination plays a key role in regulating various biological processes and is associated with several human diseases. The accurate identification of citrullination sites is crucial for elucidating the underlying molecular mechanisms of citrullination and designing drugs for related human diseases. In this study, a novel bioinformatics tool named CKSAAP_CitrSite is developed for the prediction of citrullination sites. With the assistance of support vector machine algorithm, the highlight of CKSAAP_CitrSite is to adopt the composition of k-spaced amino acid pairs surrounding a query site as input. As illustrated by 10-fold cross-validation, CKSAAP_CitrSite achieves a satisfactory performance with a Sensitivity of 77.59%, a Specificity of 95.26%, an Accuracy of 89.37% and a Matthew's correlation coefficient of 0.7566, which is much better than those of the existing prediction method. Feature analysis shows that the N-terminal space containing pairs may play an important role in the prediction of citrullination sites, and the arginines close to N-terminus tend to be citrullinated. The conclusions derived from this study could offer useful information for elucidating the molecular mechanisms of citrullination and related experimental validations. A user-friendly web-server for CKSAAP_CitrSite is available at 123.206.31.171/CKSAAP_CitrSite/.
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3.
PROMIS, global analysis of PROtein-metabolite interactions using size separation in Arabidopsis thaliana.
Veyel, D, Sokolowska, EM, Moreno, JC, Kierszniowska, S, Cichon, J, Wojciechowska, I, Luzarowski, M, Kosmacz, M, Szlachetko, J, Gorka, M, et al
The Journal of biological chemistry. 2018;(32):12440-12453
Abstract
Small molecules not only represent cellular building blocks and metabolic intermediates, but also regulatory ligands and signaling molecules that interact with proteins. Although these interactions affect cellular metabolism, growth, and development, they have been largely understudied. Herein, we describe a method, which we named PROtein-Metabolite Interactions using Size separation (PROMIS), that allows simultaneous, global analysis of endogenous protein-small molecule and of protein-protein complexes. To this end, a cell-free native lysate from Arabidopsis thaliana cell cultures was fractionated by size-exclusion chromatography, followed by quantitative metabolomic and proteomic analyses. Proteins and small molecules showing similar elution behavior, across protein-containing fractions, constituted putative interactors. Applying PROMIS to an A. thaliana extract, we ascertained known protein-protein (PPIs) and protein-metabolite (PMIs) interactions and reproduced binding between small-molecule protease inhibitors and their respective proteases. More importantly, we present examples of two experimental strategies that exploit the PROMIS dataset to identify novel PMIs. By looking for similar elution behavior of metabolites and enzymes belonging to the same biochemical pathways, we identified putative feedback and feed-forward regulations in pantothenate biosynthesis and the methionine salvage cycle, respectively. By combining PROMIS with an orthogonal affinity purification approach, we identified an interaction between the dipeptide Tyr-Asp and the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase. In summary, we present proof of concept for a powerful experimental tool that enables system-wide analysis of PMIs and PPIs across all biological systems. The dataset obtained here comprises nearly 140 metabolites and 5000 proteins, which can be mined for putative interactors.
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4.
Evaluating in Vitro Culture Medium of Gut Microbiome with Orthogonal Experimental Design and a Metaproteomics Approach.
Li, L, Zhang, X, Ning, Z, Mayne, J, Moore, JI, Butcher, J, Chiang, CK, Mack, D, Stintzi, A, Figeys, D
Journal of proteome research. 2018;(1):154-163
Abstract
In vitro culture based approaches are time- and cost-effective solutions for rapidly evaluating the effects of drugs or natural compounds against microbiomes. The nutritional composition of the culture medium is an important determinant for effectively maintaining the gut microbiome in vitro. This study combines orthogonal experimental design and a metaproteomics approach to obtaining functional insights into the effects of different medium components on the microbiome. Our results show that the metaproteomic profile respond differently to medium components, including inorganic salts, bile salts, mucin, and short-chain fatty acids. Multifactor analysis of variance further revealed significant main and interaction effects of inorganic salts, bile salts, and mucin on the different functional groups of gut microbial proteins. While a broad regulating effect was observed on basic metabolic pathways, different medium components also showed significant modulations on cell wall, membrane, and envelope biogenesis and cell motility related functions. In particular, flagellar assembly related proteins were significantly responsive to the presence of mucin. This study provides information on the functional influences of medium components on the in vitro growth of microbiome communities and gives insight on the key components that must be considered when selecting and optimizing media for culturing ex vivo microbiotas.
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5.
Proteomics as a Tool to Identify New Targets Against Aspergillus and Scedosporium in the Context of Cystic Fibrosis.
Ramirez-Garcia, A, Pellon, A, Buldain, I, Antoran, A, Arbizu-Delgado, A, Guruceaga, X, Rementeria, A, Hernando, FL
Mycopathologia. 2018;(1):273-289
Abstract
Cystic fibrosis (CF) is a genetic disorder that increases the risk of suffering microbial, including fungal, infections. In this paper, proteomics-based information was collated relating to secreted and cell wall proteins with potential medical applications from the most common filamentous fungi in CF, i.e., Aspergillus and Scedosporium/Lomentospora species. Among the Aspergillus fumigatus secreted allergens, β-1,3-endoglucanase, the alkaline protease 1 (Alp1/oryzin), Asp f 2, Asp f 13/15, chitinase, chitosanase, dipeptidyl-peptidase V (DppV), the metalloprotease Asp f 5, mitogillin/Asp f 1, and thioredoxin reductase receive a special mention. In addition, the antigens β-glucosidase 1, catalase, glucan endo-1,3-β-glucosidase EglC, β-1,3-glucanosyltransferases Gel1 and Gel2, and glutaminase A were also identified in secretomes of other Aspergillus species associated with CF: Aspergillus flavus, Aspergillus niger, Aspergillus nidulans, and Aspergillus terreus. Regarding cell wall proteins, cytochrome P450 and eEF-3 were proposed as diagnostic targets, and alkaline protease 2 (Alp2), Asp f 3 (putative peroxiredoxin pmp20), probable glycosidases Asp f 9/Crf1 and Crf2, GPI-anchored protein Ecm33, β-1,3-glucanosyltransferase Gel4, conidial hydrophobin Hyp1/RodA, and secreted aspartyl protease Pep2 as protective vaccines in A. fumigatus. On the other hand, for Scedosporium/Lomentospora species, the heat shock protein Hsp70 stands out as a relevant secreted and cell wall antigen. Additionally, the secreted aspartyl proteinase and an ortholog of Asp f 13, as well as the cell wall endo-1,3-β-D-glucosidase and 1,3-β-glucanosyl transferase, were also found to be significant proteins. In conclusion, proteins mentioned in this review may be promising candidates for developing innovative diagnostic and therapeutic tools for fungal infections in CF patients.
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6.
Insight into the biological pathways underlying fibromyalgia by a proteomic approach.
Ramírez-Tejero, JA, Martínez-Lara, E, Rus, A, Camacho, MV, Del Moral, ML, Siles, E
Journal of proteomics. 2018;:47-55
Abstract
UNLABELLED Fibromyalgia (FM) is a form of non-articular rheumatism difficult to diagnose and treat because its etiology remains still elusive. Proteomics makes possible the systematic analysis of hundreds of proteins in clinical samples. Consequently, it has become a key tool for finding altered molecular pathways in different diseases. In this context, the present study analyzes changes in the plasma proteome of patients with FM by nanoscale liquid chromatography coupled to tandem mass spectrometry. Deregulated proteins were studied using Ingenuity Pathways Analysis (IPA) and Kyoto Encyclopedia of Genes and Genomes. Conventional analytical methods were used to validate selected proteins. We found a total of 33 proteins differentially expressed in patients with FM. Haptoglobin and fibrinogen showed the highest FM/control ratio. IPA analysis revealed that the top enriched canonical pathways were acute-phase response signaling, Liver-X Receptor/Retinoid-X Receptor activation, Farnesoid-X Receptor/Retinoid-X Receptor activation, and coagulation and complement systems. The importance of inflammation in FM was corroborated by the increase in erythrocyte sedimentation rate. In conclusion, our results support the existence of a plasma protein signature of FM that involves different biological pathways all of them related to inflammation, and point to haptoglobin and fibrinogen as plausible biomarker-candidates for future studies. SIGNIFICANCE The etiology of fibromyalgia (FM) remains elusive making its diagnosis and treatment difficult. The characterization of the proteome signature of this syndrome will improve its understanding. However, to date proteomic analyses in FM are scarce. The goal of the present work is to analyse, for the first time, changes in plasma protein profiles of patients with FM in comparison to control subjects, using label free relative protein quantification by nanoscale liquid chromatography coupled to tandem mass spectrometry. Our data demonstrate the existence of a common protein signature in the plasma of patients with FM that could explain some of the symptoms associated to this syndrome. The analysis of the 33 proteins differentially expressed corroborates the crucial role of inflammation in the pathogenesis of this syndrome. The interplay of the complement and coagulation cascades contributes to the inflammatory process, while the activation of Liver-X Receptor/Retinoid-X Receptor and Farnesoid-X Receptor/Retinoid-X Receptor could attempt to alleviate it. Finally, we have identified two proteins, haptoglobin and fibrinogen, as potential biomarker-candidates of FM for future studies.
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7.
Emerging Diagnostic and Therapeutic Potentials of Human Hair Proteomics.
Adeola, HA, Van Wyk, JC, Arowolo, A, Ngwanya, RM, Mkentane, K, Khumalo, NP
Proteomics. Clinical applications. 2018;(2)
Abstract
The use of noninvasive human substrates to interrogate pathophysiological conditions has become essential in the post- Human Genome Project era. Due to its high turnover rate, and its long term capability to incorporate exogenous and endogenous substances from the circulation, hair testing is emerging as a key player in monitoring long term drug compliance, chronic alcohol abuse, forensic toxicology, and biomarker discovery, among other things. Novel high-throughput 'omics based approaches like proteomics have been underutilized globally in comprehending human hair morphology and its evolving use as a diagnostic testing substrate in the era of precision medicine. There is paucity of scientific evidence that evaluates the difference in drug incorporation into hair based on lipid content, and very few studies have addressed hair growth rates, hair forms, and the biological consequences of hair grooming or bleaching. It is apparent that protein-based identification using the human hair proteome would play a major role in understanding these parameters akin to DNA single nucleotide polymorphism profiling, up to single amino acid polymorphism resolution. Hence, this work seeks to identify and discuss the progress made thus far in the field of molecular hair testing using proteomic approaches, and identify ways in which proteomics would improve the field of hair research, considering that the human hair is mostly composed of proteins. Gaps in hair proteomics research are identified and the potential of hair proteomics in establishing a historic medical repository of normal and disease-specific proteome is also discussed.
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8.
Quantitative proteomics analysis of vitreous body from type 2 diabetic patients with proliferative diabetic retinopathy.
Li, J, Lu, Q, Lu, P
BMC ophthalmology. 2018;(1):151
Abstract
BACKGROUND To compare the abundance of vitreous proteins between the patients with proliferative diabetic retinopathy (PDR) and idiopathic macular hole (IMH). METHODS In this study, we performed mass spectrometry-based label-free quantitative proteomics analysis of vitreous samples from type 2 diabetic patients with PDR (n = 9) and IMH subjects (n = 9) and identified the abundance of 610 proteins. RESULTS Out of 610 proteins, 64 proteins (Group A) were unique to PDR patients, while 212 proteins (Group B) could be identified in IMH vitreous only. Among the other 334 proteins that could be detected in both PDR and IMH eyes, 62 proteins differed significantly (p < 0.05, fold change > 2), which included 52 proteins (Group C) and 10 proteins (Group D) over- and under-expressed in PDR vitreous compared with the control. All proteins in these four groups were counted as significant proteins in our study. CONCLUSIONS We identified and quantified 610 proteins in total, which included 338 significant proteins in our study. Protein distribution analysis demonstrated a clear separation of protein expression in PDR and IMH. The protein function analysis illustrated that immunity and transport related proteins might be associated with PDR.
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9.
PSSMSearch: a server for modeling, visualization, proteome-wide discovery and annotation of protein motif specificity determinants.
Krystkowiak, I, Manguy, J, Davey, NE
Nucleic acids research. 2018;(W1):W235-W241
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Abstract
There is a pressing need for in silico tools that can aid in the identification of the complete repertoire of protein binding (SLiMs, MoRFs, miniMotifs) and modification (moiety attachment/removal, isomerization, cleavage) motifs. We have created PSSMSearch, an interactive web-based tool for rapid statistical modeling, visualization, discovery and annotation of protein motif specificity determinants to discover novel motifs in a proteome-wide manner. PSSMSearch analyses proteomes for regions with significant similarity to a motif specificity determinant model built from a set of aligned motif-containing peptides. Multiple scoring methods are available to build a position-specific scoring matrix (PSSM) describing the motif specificity determinant model. This model can then be modified by a user to add prior knowledge of specificity determinants through an interactive PSSM heatmap. PSSMSearch includes a statistical framework to calculate the significance of specificity determinant model matches against a proteome of interest. PSSMSearch also includes the SLiMSearch framework's annotation, motif functional analysis and filtering tools to highlight relevant discriminatory information. Additional tools to annotate statistically significant shared keywords and GO terms, or experimental evidence of interaction with a motif-recognizing protein have been added. Finally, PSSM-based conservation metrics have been created for taxonomic range analyses. The PSSMSearch web server is available at http://slim.ucd.ie/pssmsearch/.
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10.
iTRAQ-Based Proteomic Analysis Reveals Protein Profile in Plasma from Children with Autism.
Shen, L, Zhang, K, Feng, C, Chen, Y, Li, S, Iqbal, J, Liao, L, Zhao, Y, Zhai, J
Proteomics. Clinical applications. 2018;(3):e1700085
Abstract
PURPOSE Autism is a childhood neurological disorder with poorly understood etiology and pathology. This study is designed to identify differentially expressed proteins that might serve as potential biomarkers for autism. EXPERIMENTAL DESIGN We perform iTRAQ (isobaric tags for relative and absolute quantitation) analysis for normal and autistic children's plasma of the same age group. RESULTS The results show that 24 differentially expressed proteins were identified between autistic subjects and controls. For the first time, differential expression of complement C5 (C5) and fermitin family homolog 3 (FERMT3) are related to autism. Five proteins, that is, complement C3 (C3), C5, integrin alpha-IIb (ITGA2B), talin-1 (TLN1), and vitamin D-binding protein (GC) were validated via enzyme-linked immunosorbent assay (ELISA). By ROC (receiver operating characteristic) analysis, combinations of these five proteins C3, C5, GC, ITGA2B, and TLN1 distinguished autistic children from healthy controls with a high AUC (area under the ROC curve) value (0.982, 95% CI, 0.957-1.000, p < 0.000). CONCLUSION These above described proteins are found involved in different pathways that have previously been linked to the pathophysiology of autism spectrum disorders (ASDs). The results strongly support that focal adhesions, acting cytoskeleton, cell adhesion, motility and migration, synaptogenesis, and complement system are involved in the pathogenesis of autism, and highlight the important role of platelet function in the pathophysiology of autism.