Small molecule metabolites: discovery of biomarkers and therapeutic targets

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 20, 2023

Metabolic abnormalities lead to the dysfunction of metabolic pathways and metabolite accumulation or deficiency which is well-recognized hallmarks diseases. Metabolite signatures that have close proximity subject's phenotypic informative dimension, are useful for predicting diagnosis prognosis diseases as well monitoring treatments. The lack early biomarkers could poor serious outcomes. Therefore, noninvasive methods with high specificity selectivity desperately needed. Small molecule metabolites-based metabolomics has become a specialized tool biomarker pathway analysis, revealing possible mechanisms human various deciphering therapeutic potentials. It help identify functional related variation delineate biochemical changes indicators pathological damage prior disease development. Recently, scientists established large number profiles reveal underlying networks target exploration in biomedicine. This review summarized analysis on potential value small-molecule candidate metabolites clinical events, may better diagnosis, prognosis, drug screening treatment. We also discuss challenges need be addressed fuel next wave breakthroughs.

Language: Английский

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Proximity Extension Assay in Combination with Next-Generation Sequencing for High-throughput Proteome-wide Analysis

Molecular & Cellular Proteomics, Journal Year: 2021, Volume and Issue: 20, P. 100168 - 100168

Published: Jan. 1, 2021

Understanding the dynamics of human proteome is crucial for developing biomarkers to be used as measurable indicators disease severity and progression, patient stratification, drug development. The Proximity Extension Assay (PEA) a technology that translates protein information into actionable knowledge by linking protein-specific antibodies DNA-encoded tags. In this report we demonstrate how have combined unique PEA with an innovative automated sample preparation high-throughput sequencing readout enabling parallel measurement nearly 1500 proteins in 96 samples generating close 150,000 data points per run. This advancement will major impact on discovery new prediction prognosis contribute development rapidly evolving fields wellness monitoring precision medicine.

Language: Английский

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Applications of multi‐omics analysis in human diseases

MedComm, Journal Year: 2023, Volume and Issue: 4(4)

Published: July 31, 2023

Multi-omics usually refers to the crossover application of multiple high-throughput screening technologies represented by genomics, transcriptomics, single-cell proteomics and metabolomics, spatial so on, which play a great role in promoting study human diseases. Most current reviews focus on describing development multi-omics technologies, data integration, particular disease; however, few them provide comprehensive systematic introduction multi-omics. This review outlines existing technical categories multi-omics, cautions for experimental design, focuses integrated analysis methods especially approach machine learning deep integration corresponding tools, medical researches (e.g., cancer, neurodegenerative diseases, aging, drug target discovery) as well open-source tools databases, finally, discusses challenges future directions precision medicine. With algorithms, important disease research, also provided detailed introduction. will guidance researchers, who are just entering into research.

Language: Английский

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Metabolomics in Diabetes and Diabetic Complications: Insights from Epidemiological Studies

Cells, Journal Year: 2021, Volume and Issue: 10(11), P. 2832 - 2832

Published: Oct. 21, 2021

The increasing prevalence of diabetes and its complications, such as cardiovascular kidney disease, remains a huge burden globally. Identification biomarkers for the screening, diagnosis, prognosis complications better understanding molecular pathways involved in development progression can facilitate individualized prevention treatment. With advancement analytical techniques, metabolomics identify quantify multiple simultaneously high-throughput manner. Providing information on underlying metabolic pathways, further mechanisms progression. application epidemiological studies have identified novel type 2 (T2D) branched-chain amino acids, metabolites phenylalanine, energy metabolism, lipid metabolism. Metabolomics also been applied to explore potential modulated by medications. Investigating using systems biology approach integrating with other omics data, genetics, transcriptomics, proteomics, clinical data present comprehensive network causal inference. In this regard, deepen understanding, help therapeutic targets, improve management T2D complications. current review focused metabolomic disease from studies, will provide brief overview investigations T2D.

Language: Английский

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SARS-CoV-2 RNAemia and proteomic trajectories inform prognostication in COVID-19 patients admitted to intensive care

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: June 7, 2021

Prognostic characteristics inform risk stratification in intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19). We obtained blood samples (n = 474) from hospitalized COVID-19 123), non-COVID-19 ICU sepsis 25) and healthy controls 30). Severe acute respiratory syndrome 2 (SARS-CoV-2) RNA was detected plasma or serum (RNAemia) of when neutralizing antibody response low. RNAemia is associated higher 28-day mortality (hazard ratio [HR], 1.84 [95% CI, 1.22-2.77] adjusted for age sex). comparable performance to the best protein predictors. Mannose binding lectin pentraxin-3 (PTX3), two activators complement pathway innate immune system, are positively mortality. Machine learning identified 'Age, RNAemia' PTX3' as binary signatures In longitudinal comparisons, have a distinct proteomic trajectory mortality, recovery many liver-derived proteins indicating survival. Finally, system galectin-3-binding (LGALS3BP) interaction partners SARS-CoV-2 spike glycoprotein. LGALS3BP overexpression inhibits spike-pseudoparticle uptake spike-induced cell-cell fusion vitro.

Language: Английский

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Soluble Urokinase Plasminogen Activator Receptor (suPAR) as a Biomarker of Systemic Chronic Inflammation

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Dec. 2, 2021

Systemic chronic inflammation (SCI) is persistent, health-damaging, low-grade that plays a major role in immunosenescence and development progression of many diseases. But currently, there are no recognized standard biomarkers to assess SCI levels alone, typically measured by combining acute infection, e.g., CRP, IL-6, TNFα. In this review, we highlight 10 properties characteristics shared the blood protein soluble urokinase plasminogen activator receptor (suPAR) SCI, supporting argument suPAR biomarker SCI: (1) Expression release upregulated immune activation; (2) uPAR exert pro-inflammatory functions; (3) associated with amount circulating cells; (4) Blood correlate established inflammatory biomarkers; (5) minimally affected changes short-term influences, contrast currently used markers systemic inflammation; (6) Like non-specifically multiple diseases; (7) both predict morbidity mortality; (8) share same risk factors; (9) factors outcomes above beyond other (10) The level can be reduced anti-inflammatory interventions treatment disease. Assessing has potential inform for mortality. newer which may, fact, since it stably shares as age-related elevated predicts There strong evidence prognostic marker adverse events, morbidity, It activity prognosis across diverse conditions, including kidney disease, cardiovascular cancer, diabetes, disorders. Thus, think likely represents common underlying disease-process is, SCI. We review literature propose research agenda help test hypothesis indexes becoming new gold measuring

Language: Английский

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The role of machine learning to boost the bioenergy and biofuels conversion

Bioresource Technology, Journal Year: 2021, Volume and Issue: 343, P. 126099 - 126099

Published: Oct. 8, 2021

Language: Английский

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OmicsNet 2.0: a web-based platform for multi-omics integration and network visual analytics

Nucleic Acids Research, Journal Year: 2022, Volume and Issue: 50(W1), P. W527 - W533

Published: May 5, 2022

Abstract Researchers are increasingly seeking to interpret molecular data within a multi-omics context gain more comprehensive picture of their study system. OmicsNet (www.omicsnet.ca) is web-based tool developed allow users easily build, visualize, and analyze networks rich relationships among lists ‘omics features interest. Three major improvements have been introduced in 2.0, which include: (i) enhanced network visual analytics with eleven 2D graph layout options novel 3D module layout; (ii) support for three new types: single nucleotide polymorphism (SNP) list from genetic variation studies; taxon microbiome profiling studies, as well liquid chromatography–mass spectrometry (LC–MS) peaks untargeted metabolomics; (iii) measures improve research reproducibility by coupling R command history the release companion OmicsNetR package, generation persistent links share interactive views. We performed case using obtained recent large-scale investigation on inflammatory bowel disease (IBD) demonstrated that was able quickly create meaningful facilitate hypothesis mechanistic insights.

Language: Английский

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Proteomics and lipidomics in atherosclerotic cardiovascular disease risk prediction

European Heart Journal, Journal Year: 2023, Volume and Issue: 44(18), P. 1594 - 1607

Published: March 29, 2023

Given the limited accuracy of clinically used risk scores such as Systematic COronary Risk Evaluation 2 system and Second Manifestations ARTerial disease scores, novel algorithms determining an individual's susceptibility future incident or recurrent atherosclerotic cardiovascular (ASCVD) are urgently needed. Due to major improvements in assay techniques, multimarker proteomic lipidomic panels hold promise be reliably assessed a high-throughput routine. Novel machine learning-based approaches have facilitated use this high-dimensional data resulting from these analyses for ASCVD prediction. More than dozen large-scale retrospective studies using different sets biomarkers statistical methods consistently demonstrated additive prognostic value over traditionally clinical scores. Prospective needed determine utility biomarker panel stratification. When combined with genetic predisposition captured polygenic actual phenotype observed coronary artery imaging, proteomics lipidomics can advance understanding complex multifactorial causes underlying risk.

Language: Английский

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Cardiometabolic health, diet and the gut microbiome: a meta-omics perspective

Nature Medicine, Journal Year: 2023, Volume and Issue: 29(3), P. 551 - 561

Published: March 1, 2023

Language: Английский

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