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Nature Communications Sep 2023COVID-19 is characterised by systemic immunological perturbations in the human body, which can lead to multi-organ damage. Many of these processes are considered to be... (Meta-Analysis)
Meta-Analysis
COVID-19 is characterised by systemic immunological perturbations in the human body, which can lead to multi-organ damage. Many of these processes are considered to be mediated by the blood. Therefore, to better understand the systemic host response to SARS-CoV-2 infection, we performed systematic analyses of the circulating, soluble proteins in the blood through global proteomics by mass-spectrometry (MS) proteomics. Here, we show that a large part of the soluble blood proteome is altered in COVID-19, among them elevated levels of interferon-induced and proteasomal proteins. Some proteins that have alternating levels in human cells after a SARS-CoV-2 infection in vitro and in different organs of COVID-19 patients are deregulated in the blood, suggesting shared infection-related changes.The availability of different public proteomic resources on soluble blood proteome alterations leaves uncertainty about the change of a given protein during COVID-19. Hence, we performed a systematic review and meta-analysis of MS global proteomics studies of soluble blood proteomes, including up to 1706 individuals (1039 COVID-19 patients), to provide concluding estimates for the alteration of 1517 soluble blood proteins in COVID-19. Finally, based on the meta-analysis we developed CoViMAPP, an open-access resource for effect sizes of alterations and diagnostic potential of soluble blood proteins in COVID-19, which is publicly available for the research, clinical, and academic community.
Topics: Humans; COVID-19; Proteome; Proteomics; SARS-CoV-2; Cytoplasm
PubMed: 37739942
DOI: 10.1038/s41467-023-41159-z -
Metabolic Syndrome and Related Disorders Dec 2022This study aims to systematically evaluate the association between metabolic syndrome (MS) and pulmonary function through meta-analysis. Electronic databases,... (Meta-Analysis)
Meta-Analysis
This study aims to systematically evaluate the association between metabolic syndrome (MS) and pulmonary function through meta-analysis. Electronic databases, including PubMed, Embase, Web of Science, and Cochrane Library, were systematically searched to obtain articles associated with MS and lung function published before December 31, 2021. According to the including and excluding criteria, certain studies were obtained and data were extracted. The Newcastle Ottawa Scale was used to evaluate the quality of the studies. A pooled standardized mean difference (SMD) was calculated by means of random-effects meta-analysis. Different effect models were used according to the heterogeneity. Meta-regression and sensitivity analyses were performed to examine the possible sources of heterogeneity. The Begg's funnel plot and Egger's test were used to evaluate publication bias. Analyses were performed using Stata MP, version14.0 (StataCorp LP, College Station, TX, USA). A total of 15 studies, involving 10,285 cases of MS and 25,416 cases of control, were included in this meta-analysis on the relationship between MS and forced vital capacity (FVC). The pooled SMD for FVC was -0.247 (95% CI = -0.327 to -0.2167, < 0.001) using random effect model, indicating the decrease of FVC in the patients with MS. In the same studies, the pooled SMD for forced expiratory volume in 1 sec (FEV) was -0.205 (95% CI = -0.3278 to -0.133, < 0.001), indicating the decrease of FEV also existed in the MS cases. A total of 13 studies, involving 8167 cases of MS and 19,788 cases of control, were included in this meta-analysis on the relationship between MS and FEV/FVC. The pooled SMD for FEV/FVC was 0.011 (95% CI = -0.072 to 0.093, = 0.798) using random effect model, indicating that there was no significant difference between the patients with MS and the control. After introducing the diastolic blood pressure and glycemia into the regression model of the relationship between MS and FVC, the variance of the studies (tau2) decreased from 0.0190 to 0.006694 and 0.007205, which could explain 66.70% and 78.04% of the sources of heterogeneity, and the values were 0.038 and 0.023. The results suggested that hypertension (diastolic pressure) and hyperglycemia were the factors linked to the heterogeneity among the included studies on both FVC and FEV. The Begg's funnel plot and Egger's test both showed no evidence of publication bias. Our results show that FVC and FEV decrease in MS patients, while FEV/FVC has no significant difference compared with the control group. It indicates that the patients with MS have restrictive ventilatory functional disturbance. Meta-regression analysis suggests that hypertension (diastolic pressure) and hyperglycemia are the factors linked to the heterogeneity among the included studies on both FVC and FEV.
Topics: Humans; Metabolic Syndrome; Lung; Forced Expiratory Volume; Hypertension; Hyperglycemia
PubMed: 36125502
DOI: 10.1089/met.2022.0045 -
Wiener Klinische Wochenschrift Dec 2016Osteoporosis is the most frequent bone metabolic disease. In order to improve early detection, prediction, prevention, diagnosis, and treatment of the disease, a new... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Osteoporosis is the most frequent bone metabolic disease. In order to improve early detection, prediction, prevention, diagnosis, and treatment of the disease, a new model of P4 medicine (personalized, predictive, preventive, and participatory medicine) could be applied. The aim of this work was to systematically review the publications of four different types of "omics" studies related to osteoporosis, in order to discover novel predictive, preventive, diagnostic, and therapeutic targets for better management of the geriatric population.
METHODS
To systematically search the PubMed database, we created specific groups of criteria for four different types of "omics" information on osteoporosis: genomic, transcriptomic, proteomic, and metabolomic. We then analyzed the intersections between them in order to find correlations and common pathways or molecules with important roles in osteoporosis, and with a potential application in disease prediction, prevention, diagnosis, or treatment.
RESULTS
Altogether, 180 publications of "omics" studies in the field of osteoporosis were found and reviewed at first selection. After introducing the inclusion and exclusion criteria (the secondary selection), 46 papers were included in the systematic review.
CONCLUSIONS
The intersection of reviewed papers identified five genes (ESR1, IBSP, CTNNB1, SOX4, and IDUA) and processes like the Wnt pathway, JAK/STAT signaling, and ERK/MAPK, which should be further validated for their predictive, diagnostic, or other clinical value in osteoporosis. Such molecular insights will enable us to fit osteoporosis into the P4 strategy and could increase the effectiveness of disease prediction and prevention, with a decrease in morbidity in the geriatric population.
Topics: Aged; Aged, 80 and over; Female; Genetic Markers; Genetic Predisposition to Disease; Genetic Testing; Geriatric Assessment; Humans; Male; Osteoporosis; Precision Medicine; Prevalence; Risk Factors
PubMed: 27873024
DOI: 10.1007/s00508-016-1125-3 -
Frontiers in Immunology 2022Multiple sclerosis (MS) is an inflammatory demyelinating and degenerative disease of the central nervous system (CNS). Although inflammatory responses are efficiently...
Multiple sclerosis (MS) is an inflammatory demyelinating and degenerative disease of the central nervous system (CNS). Although inflammatory responses are efficiently treated, therapies for progression are scarce and suboptimal, and biomarkers to predict the disease course are insufficient. Cure or preventive measures for MS require knowledge of core pathological events at the site of the tissue damage. Novelties in systems biology have emerged and paved the way for a more fine-grained understanding of key pathological pathways within the CNS, but they have also raised questions still without answers. Here, we systemically review the power of tissue and single-cell/nucleus CNS omics and discuss major gaps of integration into the clinical practice. Systemic search identified 49 transcriptome and 11 proteome studies of the CNS from 1997 till October 2021. Pioneering molecular discoveries indicate that MS affects the whole brain and all resident cell types. Despite inconsistency of results, studies imply increase in transcripts/proteins of semaphorins, heat shock proteins, myelin proteins, apolipoproteins and HLAs. Different lesions are characterized by distinct astrocytic and microglial polarization, altered oligodendrogenesis, and changes in specific neuronal subtypes. In all white matter lesion types, are highly expressed, and STAT6- and TGFβ-signaling are increased. In the grey matter lesions, TNF-signaling seems to drive cell death, and especially -expressing neurons may be susceptible to neurodegeneration. The vast heterogeneity at both cellular and lesional levels may underlie the clinical heterogeneity of MS, and it may be more complex than the current disease phenotyping in the clinical practice. Systems biology has not solved the mystery of MS, but it has discovered multiple molecules and networks potentially contributing to the pathogenesis. However, these results are mostly descriptive; focused functional studies of the molecular changes may open up for a better interpretation. Guidelines for acceptable quality or awareness of results from low quality data, and standardized computational and biological pipelines may help to overcome limited tissue availability and the "snap shot" problem of omics. These may help in identifying core pathological events and point in directions for focus in clinical prevention.
Topics: Brain; Humans; Multiple Sclerosis; Proteome; Transcriptome; White Matter
PubMed: 35309325
DOI: 10.3389/fimmu.2022.761225 -
Biomolecules Nov 2023Mitochondria are ancient endosymbiotic double membrane organelles that support a wide range of eukaryotic cell functions through energy, metabolism, and cellular... (Review)
Review
Mitochondria are ancient endosymbiotic double membrane organelles that support a wide range of eukaryotic cell functions through energy, metabolism, and cellular control. There are over 1000 known proteins that either reside within the mitochondria or are transiently associated with it. These mitochondrial proteins represent a functional subcellular protein network (mtProteome) that is encoded by mitochondrial and nuclear genomes and significantly varies between cell types and conditions. In neurons, the high metabolic demand and differential energy requirements at the synapses are met by specific modifications to the mtProteome, resulting in alterations in the expression and functional properties of the proteins involved in energy production and quality control, including fission and fusion. The composition of mtProteomes also impacts the localization of mitochondria in axons and dendrites with a growing number of neurodegenerative diseases associated with changes in mitochondrial proteins. This review summarizes the findings on the composition and properties of mtProteomes important for mitochondrial energy production, calcium and lipid signaling, and quality control in neural cells. We highlight strategies in mass spectrometry (MS) proteomic analysis of mtProteomes from cultured cells and tissue. The research into mtProteome composition and function provides opportunities in biomarker discovery and drug development for the treatment of metabolic and neurodegenerative disease.
Topics: Humans; Proteome; Neurodegenerative Diseases; Proteomics; Mitochondria; Neurons; Mitochondrial Proteins
PubMed: 38002320
DOI: 10.3390/biom13111638 -
Frontiers in Immunology 2023Sjögren's syndrome (SS) is a systemic autoimmune disease, which affects the exocrine glands leading to glandular dysfunction and, particularly, symptoms of oral and...
INTRODUCTION
Sjögren's syndrome (SS) is a systemic autoimmune disease, which affects the exocrine glands leading to glandular dysfunction and, particularly, symptoms of oral and ocular dryness. The aetiology of SS remains unclear, and the disease lacks distinctive clinical features. The current diagnostic work-up is complex, invasive and often time-consuming. Thus, there is an emerging need for identifying disease-specific and, ideally, non-invasive immunological and molecular biomarkers that can simplify the diagnostic process, allow stratification of patients, and assist in monitoring the disease course and outcome of therapeutic intervention in SS.
METHODS
This systematic review addresses the use of proteomics and miRNA-expression profile analyses in this regard.
RESULTS AND DISCUSSION
Out of 272 papers that were identified and 108 reviewed, a total of 42 papers on proteomics and 23 papers on miRNA analyses in saliva, blood and salivary gland tissue were included in this review. Overall, the proteomic and miRNA studies revealed considerable variations with regard to candidate biomarker proteins and miRNAs, most likely due to variation in sample size, processing and analytical methods, but also reflecting the complexity of SS and patient heterogeneity. However, interesting novel knowledge has emerged and further validation is needed to confirm their potential role as biomarkers in SS.
Topics: Humans; Sjogren's Syndrome; MicroRNAs; Proteomics; Saliva; Biomarkers
PubMed: 37275849
DOI: 10.3389/fimmu.2023.1183195 -
Statistics in Medicine Feb 2023This review condenses the knowledge on variable selection methods implemented in R and appropriate for datasets with grouped features. The focus is on regularized... (Review)
Review
This review condenses the knowledge on variable selection methods implemented in R and appropriate for datasets with grouped features. The focus is on regularized regressions identified through a systematic review of the literature, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 14 methods are discussed, most of which use penalty terms to perform group variable selection. Depending on how the methods account for the group structure, they can be classified into knowledge and data-driven approaches. The first encompass group-level and bi-level selection methods, while two-step approaches and collinearity-tolerant methods constitute the second category. The identified methods are briefly explained and their performance compared in a simulation study. This comparison demonstrated that group-level selection methods, such as the group minimax concave penalty, are superior to other methods in selecting relevant variable groups but are inferior in identifying important individual variables in scenarios where not all variables in the groups are predictive. This can be better achieved by bi-level selection methods such as group bridge. Two-step and collinearity-tolerant approaches such as elastic net and ordered homogeneity pursuit least absolute shrinkage and selection operator are inferior to knowledge-driven methods but provide results without requiring prior knowledge. Possible applications in proteomics are considered, leading to suggestions on which method to use depending on existing prior knowledge and research question.
Topics: Humans; Computer Simulation
PubMed: 36546512
DOI: 10.1002/sim.9620 -
Cancers Oct 2023The accurate diagnosis of small-cell lung cancer (SCLC) is crucial, as treatment strategies differ from those of other lung cancers. This systematic review aims to... (Review)
Review
The accurate diagnosis of small-cell lung cancer (SCLC) is crucial, as treatment strategies differ from those of other lung cancers. This systematic review aims to identify proteins differentially expressed in SCLC compared to normal lung tissue, evaluating their potential utility in diagnosing and prognosing the disease. Additionally, the study identifies proteins differentially expressed between SCLC and large cell neuroendocrine carcinoma (LCNEC), aiming to discover biomarkers distinguishing between these two subtypes of neuroendocrine lung cancers. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a comprehensive search was conducted across PubMed/MEDLINE, Scopus, Embase, and Web of Science databases. Studies reporting proteomics information and confirming SCLC and/or LCNEC through histopathological and/or cytopathological examination were included, while review articles, non-original articles, and studies based on animal samples or cell lines were excluded. The initial search yielded 1705 articles, and after deduplication and screening, 16 articles were deemed eligible. These studies revealed 117 unique proteins significantly differentially expressed in SCLC compared to normal lung tissue, along with 37 unique proteins differentially expressed between SCLC and LCNEC. In conclusion, this review highlights the potential of proteomics technology in identifying novel biomarkers for diagnosing SCLC, predicting its prognosis, and distinguishing it from LCNEC.
PubMed: 37894372
DOI: 10.3390/cancers15205005 -
Frontiers in Genetics 2023In the last years, liquid biopsy gained increasing clinical relevance for detecting and monitoring several cancer types, being minimally invasive, highly informative and... (Review)
Review
In the last years, liquid biopsy gained increasing clinical relevance for detecting and monitoring several cancer types, being minimally invasive, highly informative and replicable over time. This revolutionary approach can be complementary and may, in the future, replace tissue biopsy, which is still considered the gold standard for cancer diagnosis. "Classical" tissue biopsy is invasive, often cannot provide sufficient bioptic material for advanced screening, and can provide isolated information about disease evolution and heterogeneity. Recent literature highlighted how liquid biopsy is informative of proteomic, genomic, epigenetic, and metabolic alterations. These biomarkers can be detected and investigated using single-omic and, recently, in combination through multi-omic approaches. This review will provide an overview of the most suitable techniques to thoroughly characterize tumor biomarkers and their potential clinical applications, highlighting the importance of an integrated multi-omic, multi-analyte approach. Personalized medical investigations will soon allow patients to receive predictable prognostic evaluations, early disease diagnosis, and subsequent treatments.
PubMed: 37077538
DOI: 10.3389/fgene.2023.1152470 -
Frontiers in Immunology 2024Anaphylaxis manifests as a severe immediate-type hypersensitivity reaction initiated through the immunological activation of target B-cells by allergens, leading to the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Anaphylaxis manifests as a severe immediate-type hypersensitivity reaction initiated through the immunological activation of target B-cells by allergens, leading to the release of mediators. However, the well-known underlying pathological mechanisms do not fully explain the whole variety of clinical and immunological presentations. We performed a systemic review of proteomic and metabolomic studies and analyzed the extracted data to improve our understanding and identify potential new biomarkers of anaphylaxis.
METHODS
Proteomic and metabolomic studies in both human subjects and experimental models were extracted and selected through a systematic search conducted on databases such as PubMed, Scopus, and Web of Science, up to May 2023.
RESULTS
Of 137 retrieved publications, we considered 12 for further analysis, including seven on proteome analysis and five on metabolome analysis. A meta-analysis of the four human studies identified 118 proteins with varying expression levels in at least two studies. Beside established pathways of mast cells and basophil activation, functional analysis of proteomic data revealed a significant enrichment of biological processes related to neutrophil activation and platelet degranulation and metabolic pathways of arachidonic acid and icosatetraenoic acid. The pathway analysis highlighted also the involvement of neutrophil degranulation, and platelet activation. Metabolome analysis across different models showed 13 common metabolites, including arachidonic acid, tryptophan and lysoPC(18:0) lysophosphatidylcholines.
CONCLUSION
Our review highlights the underestimated role of neutrophils and platelets in the pathological mechanisms of anaphylactic reactions. These findings, derived from a limited number of publications, necessitate confirmation through human studies with larger sample sizes and could contribute to the development of new biomarkers for anaphylaxis.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024506246.
Topics: Humans; Anaphylaxis; Arachidonic Acid; Proteomics; Allergens; Biomarkers
PubMed: 38384462
DOI: 10.3389/fimmu.2024.1328212