With the development of modern high-throughput omic measurement platforms, it has become essential for biomedical studies to undertake an integrative (combined) approach to fully utilise these data ...to gain insights into biological systems. Data from various omics sources such as genetics, proteomics, and metabolomics can be integrated to unravel the intricate working of systems biology using machine learning-based predictive algorithms. Machine learning methods offer novel techniques to integrate and analyse the various omics data enabling the discovery of new biomarkers. These biomarkers have the potential to help in accurate disease prediction, patient stratification and delivery of precision medicine. This review paper explores different integrative machine learning methods which have been used to provide an in-depth understanding of biological systems during normal physiological functioning and in the presence of a disease. It provides insight and recommendations for interdisciplinary professionals who envisage employing machine learning skills in multi-omics studies.
•Machine learning methods are novel techniques to integrate omics datasets•Recently, publications based on ‘multi-omics integration’ have gained popularity•Integration of omics data using concatenation, model- or transformation-based methods•Multi-omics studies offer a more comprehensive view of complex diseases•Recommendation flowchart included for interdisciplinary professionals
Environmental stress is a significant contributor to the development of inflammatory bowel disease (IBD). The involvement of temperature stimulation in the development of IBD remains uncertain. Our ...preliminary statistical data suggest that the prevalence of IBD is slightly lower in colder regions compared to non-cold regions. The observation indicates that temperature changes may play a key role in the occurrence and progression of IBD. Here, we hypothesized that cold stress has a protective effect on IBD.
The cold exposure model for mice was placed in a constant temperature and humidity chamber, maintained at a temperature of 4 °C. Colitis models were induced in the mice using TNBS or DSS. To promote the detection methods more clinically, fluorescence confocal endoscopy was used to observe the mucosal microcirculation status of the colon in the live model. Changes in the colonic wall of the mice were detected using 9.4 T Magnetic Resonance Imaging (MRI) imaging and in vivo fluorescence imaging. Hematoxylin and eosin (H&E) and Immunofluorescence (IF) staining confirmed the pathological alterations in the colons of sacrificed mice. Molecular changes at the protein level were assessed through Western blotting and Enzyme-Linked Immunosorbent Assay (ELISA) assays. RNA sequencing (RNA-seq) and metabolomics (n = 18) were jointly analyzed to investigate the biological changes in the colon of mice treated by cold exposure.
Cold exposure decreased the pathologic and disease activity index scores in a mouse model. Endomicroscopy revealed that cold exposure preserved colonic mucosal microcirculation, and 9.4 T MRI imaging revealed alleviation of intestinal wall thickness. In addition, the expression of the TLR4 and PP65 proteins was downregulated and epithelial cell junctions were strengthened after cold exposure. Intriguingly, we found that cold exposure reversed the decrease in ZO-1 and occludin protein levels in dextran sulfate sodium (DSS)- and trinitrobenzenesulfonic acid-induced colitis mouse models. Multi-omics analysis revealed the biological landscape of DSS-induced colitis under cold exposure and identified that the peroxisome proliferator-activated receptor (PPAR) signaling pathway mediates the effects of cold on colitis. Subsequent administration of rosiglitazone (PPAR agonist) enhanced the protective effect of cold exposure on colitis, whereas GW9662 (PPAR antagonist) administration mitigated these protective effects. Overall, cold exposure ameliorated the progression of mouse colitis through the PPARγ/NF-κB signaling axis and preserved the intestinal mucosal barrier.
Our study provides a mechanistic link between intestinal inflammation and cold exposure, providing a theoretical framework for understanding the differences in the prevalence of IBD between the colder regions and non-cold regions, and offering new insights into IBD therapy.
Particulate matter (PM) is a huge environmental threat and is of major public concern. Oxidative stress and systemic inflammation are known factors that contribute to PM- related damage; however, a ...systematic understanding of the deleterious pulmonary effects of PM using multi-omics analysis is lacking. In this study, we performed transcriptomic, proteomic, and metabolomic analyses in a mouse model exposed to PM for three months to identify molecular changes in lung tissues. We identified 1690 genes, 326 proteins, and 67 metabolites exhibiting significant differences between PM-challenged and control mice (p < 0.05). Differentially expressed genes and proteins regulated in PM-challenged mice were involved in lipid metabolism and in the immune and inflammatory response processes. Moreover, a comprehensive analysis of transcript, protein, and metabolite datasets revealed that the genes, proteins, and metabolites in the PM-treated group were involved in lysosomal function and lipid metabolism. Specifically, Cathepsin D (Ctsd), Ferritin light chain (Ftl), Lactotransferrin (Ltf), Lipocalin 2 (Lcn2), and Prosaposin (Psap) were major proteins/genes associated with PM-induced pulmonary damage, while two lipid molecules PC (18:1(11Z)/16:0) and PA (16:0/18:1(11Z)) were major metabolites related to PM-induced pulmonary injury. In summary, lipid metabolism might be used as successful precautions and therapeutic targets in PM-induced pulmonary injury to maintain the stability of cellular lysosomal function.
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•A multi-omics approach was used to identify molecular changes in mouse lung tissues.•PM exposure impairs lung structure and inflammatory reactions in the mouse lungs.•Sub-chronic exposure to PM causes lung injury by disturbing lysosomal function and lipid metabolism homeostasis.•Different pathways are triggered in mouse lung tissues in response to PM exposure.
Osteoporosis (OP) is a metabolic bone disease that can lead to major health challenges. The theory of Traditional Chinese medicine believes that kidney-Yin deficiency (KYD) is the main cause of ...postmenopausal osteoporosis. This study was aimed to investigate the effect of EZW on anti-osteoporosis with KYD, and explore potential mechanisms from the perspective of the kidney, bone and bone marrow through analysis of metabolomics and proteomics. The model of OP with KYD was established by rats treated with bilateral ovariectomy (OVX), and then given intragastric administration of thyroid and reserpine to induce. Micro-CT was applied to determine the microstructures of bone. Serum levels associated with bone turnover markers and kidney-Yin deficiency were detected by enzyme-linked immunosorbent (ELISA) assay. The differential metabolites in the kidney, bone and bone marrow were analyzed by metabolomics. The differentially expressed proteins in these three tissues were detected via proteomics. The findings suggested that EZW could alleviate a variety of metabolites and proteins among the kidney, bone and bone marrow, primarily in amino acid metabolism, carbohydrate metabolism, nucleotide metabolism and lipid metabolism, thus leading to improvements of OP with KYD, which provided theoretical basis for clinical treatment of EZW on OP with KYD.
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•EZW exerted anti-OP with KYD effects via pharmacodynamics evaluations.•EZW regulated metabolites and proteins of kidney, bone, bone marrow in OP with KYD.•EZW against OP with KYD was involved in amino acid metabolism and lipid metabolism.
•Oxidation promoted the formation of volatile flavor compounds such as heptanal, octanal, nonanal, 2,3-glutaraldehyde, 3-hydroxy-2-butanone.•The content of 3-dehydrocinchoninic acid, tyrosine, etc. ...decreased gradually with the increase of oxidation time.•Octanal, nonanal and benzaldehyde maybe related to the formation of off-odor or acidification during oxidation of yak meat.•Oxidation-induced fatty acid and amino acid metabolism is the main cause of flavor changes in yak meat.
Hydroxyl radical system combined with GC-IMS and metabolomics were used to assess the effect of oxidation on the formation of volatile flavor emitted from yak meat. The formation of volatile compounds, including heptanal, octanal, nonanal, 2,3-glutaraldehyde, 3-hydroxy-2-butanone, etc. were promoted by oxidation. Among them, 2,3-pentanedione and 3-hydroxy-2-butanone, etc. maybe contributed most to the overall aroma of yak meat, while octanal, nonanal and benzaldehyde maybe related to the formation of off-odor or acidification. Meanwhile, the content of metabolites such as oleic acid, linoleic acid, etc. fatty acids and 3-dehydromangiferic acid, tyrosine were increased or decreased with the time of oxidation. More importantly, the formation of most flavor components in yak meat during the course of oxidation were related to stearidonic acid, acetylleucine, dehydroshikimate, 6-phosphate-glucose etc. differential metabolic components. Moreover, starch and sucrose metabolism (prediction), and amino acid metabolism (enrichment) etc. pathways maybe related with the process of oxidation.
Psoriasis is a chronic and recurrent inflammatory skin disorder. The primary manifestation of psoriasis arises from disturbances in the cutaneous immune microenvironment, but the specific functions ...of the cellular components within this microenvironment remain unknown. Recent advancements in single-cell technologies have enabled the detection of multi-omics at the level of individual cells, including single-cell transcriptome, proteome, and metabolome, which have been successfully applied in studying autoimmune diseases, and other pathologies. These techniques allow the identification of heterogeneous cell clusters and their varying contributions to disease development. Considering the immunological traits of psoriasis, an in-depth exploration of immune cells and their interactions with cutaneous parenchymal cells can markedly advance our comprehension of the mechanisms underlying the onset and recurrence of psoriasis. In this comprehensive review, we present an overview of recent applications of single-cell technologies in psoriasis, aiming to improve our understanding of the underlying mechanisms of this disorder.
•A comprehensive overview of single-cell technology in psoriasis is provided.•The heterogeneity of the immune microenvironment in psoriasis is summarized.•Psoriatic inflamed cells display diverse subtypes and distinct functions.•Single-cell technology has redefined the psoriatic immunological landscape.
Research on astronaut health and model organisms have revealed six features of spaceflight biology that guide our current understanding of fundamental molecular changes that occur during space ...travel. The features include oxidative stress, DNA damage, mitochondrial dysregulation, epigenetic changes (including gene regulation), telomere length alterations, and microbiome shifts. Here we review the known hazards of human spaceflight, how spaceflight affects living systems through these six fundamental features, and the associated health risks of space exploration. We also discuss the essential issues related to the health and safety of astronauts involved in future missions, especially planned long-duration and Martian missions.
An international group of spaceflight researchers detail how spaceflight affects human biology from the molecular to physiological level and identify key challenges for making space exploration compatible with human health.
Recent advances in high-throughput technologies have enabled the profiling of multiple layers of a biological system, including DNA sequence data (genomics), RNA expression levels (transcriptomics), ...and metabolite levels (metabolomics). This has led to the generation of vast amounts of biological data that can be integrated in so-called multi-omics studies to examine the complex molecular underpinnings of health and disease. Integrative analysis of such datasets is not straightforward and is particularly complicated by the high dimensionality and heterogeneity of the data and by the lack of universal analysis protocols. Previous reviews have discussed various strategies to address the challenges of data integration, elaborating on specific aspects, such as network inference or feature selection techniques. Thereby, the main focus has been on the integration of two omics layers in their relation to a phenotype of interest. In this review we provide an overview over a typical multi-omics workflow, focusing on integration methods that have the potential to combine metabolomics data with two or more omics. We discuss multiple integration concepts including data-driven, knowledge-based, simultaneous and step-wise approaches. We highlight the application of these methods in recent multi-omics studies, including large-scale integration efforts aiming at a global depiction of the complex relationships within and between different biological layers without focusing on a particular phenotype.
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•Multi-omics studies can unravel the complex molecular underpinnings of diseases.•Data availability and study aims influence the selection of the integration strategy.•Knowledge-based integration can enhance the biological interpretability of results.•Data-driven integration can infer relationships between uncharacterized molecules.•Network-based, hybrid integration strategies combine the strengths of both.
The current consensus recognizes four main medulloblastoma subgroups (wingless, Sonic hedgehog, group 3 and group 4). While medulloblastoma subgroups have been characterized extensively at the ...(epi-)genomic and transcriptomic levels, the proteome and phosphoproteome landscape remain to be comprehensively elucidated. Using quantitative (phospho)-proteomics in primary human medulloblastomas, we unravel distinct posttranscriptional regulation leading to highly divergent oncogenic signaling and kinase activity profiles in groups 3 and 4 medulloblastomas. Specifically, proteomic and phosphoproteomic analyses identify aberrant ERBB4-SRC signaling in group 4. Hence, enforced expression of an activated SRC combined with p53 inactivation induces murine tumors that resemble group 4 medulloblastoma. Therefore, our integrative proteogenomics approach unveils an oncogenic pathway and potential therapeutic vulnerability in the most common medulloblastoma subgroup.
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•Highly divergent posttranscriptional pathway regulation in MB subgroups•Phosphoproteomic profiles reveal specific kinase activity in MB subgroups•Identification of aberrant ERBB4-SRC signaling as a hallmark of group 4 MBs•Over expression of activated SRC in the developing cerebellum induces MB
Using proteomic analyses, Forget et al. unravel divergent oncogenic signaling and kinase activity profiles in groups 3 and 4 medulloblastomas (MB) and identify aberrant ERBB4-SRC signaling in group 4. Expression of an activated SRC combined with p53 inactivation induces murine tumors that resemble group 4 MB.
Background
Eosinophils are multifunctional granulocytes capable of releasing various cytokines, chemokines, and lipid mediators. We previously reported dysregulated fatty acid metabolism in ...peripheral blood‐derived eosinophils from patients with severe asthma. However, functional characteristics of eosinophils present in allergic inflammatory tissues remain largely uncharacterized.
Methods
We established a method for isolating CD69hi CCR3low CXCR4‐ siglec‐8int eosinophils from nasal polyps of patients with eosinophilic rhinosinusitis (NP‐EOS). Multi‐omics analysis including lipidomics, proteomics, and transcriptomics was performed to analyze NP‐EOS as compared to peripheral blood‐derived eosinophils from healthy subjects (PB‐EOS).
Results
Lipidomic analysis revealed impaired synthesis of prostaglandins and 15‐lipoxygenase (15‐LOX)‐derived mediators, and selective upregulation of leukotriene D4 production. Furthermore, proteomics and transcriptomics revealed changes in the expression of specific enzymes (GGT5, DPEP2, and 15‐LOX) responsible for dysregulated lipid metabolism. Ingenuity pathway analysis indicated the importance of type 2 cytokines and pattern recognition receptor pathways. Stimulation of PB‐EOS with eosinophil activators IL‐5, GM‐CSF, and agonists of TLR2 and NOD2 mimicked the observed changes in lipid metabolism.
Conclusion
Inflammatory tissue‐derived eosinophils possess a specific phenotype with dysregulated fatty acid metabolism that may be targeted therapeutically to control eosinophilic inflammatory diseases.
Eosinophils isolated from nasal polyps of patients with eosinophilic rhinosinusitis possess dysregulated fatty acid metabolism. Of the CysLT (cysteinyl leukotriene) biosynthetic pathway metabolites, LTD4 production is selectively enhanced with increased expression of GGT5 (gamma‐glutamyl trasferase‐5) and decreased expression of DPEP2 (dipeptidase‐2). Type 2 cytokines (IL‐5 and GM‐CSF) and agonists of TLR2 and NOD2 induce similar changes of fatty acid metabolism.COX: Cyclooxygenase; CRS: Chronic rhinosinusitis; DPEP2: Dipeptidase‐2; GGT5: Gamma‐glutamyl trasferase‐5; GM‐CSF: Granulocyte‐macrophage colony‐stimulating factor; ILC2: Type 2 innate lymphoid cells; LTC4: Leukotriene C4; LTD4: Leukotriene D4; LTE4: Leukotriene E4; LXA4: Lipoxin A4; NOD2: Nucleotide binding oligomerization domain containing 2; PGE2: Prostaglandin E2; Th2: Type 2 helper T cells; TLR2: Toll‐like receptor 2
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