PubMed
Metabolomics and Transcriptomics Reveal the Role of the Terpene Biosynthetic Pathway in the Mechanism of Insect Resistance in Solanum habrochaites
J Agric Food Chem. 2025 Feb 25. doi: 10.1021/acs.jafc.4c10397. Online ahead of print.ABSTRACTTerpenes are a large variety of natural organic compounds that can enhance the resistance of plants to phytophagous insects through induction. In this study, differential expression genes and metabolites of Alice Craig (AC) and Solanum habrochaite (SH) were screened and analyzed by transcriptomics and metabolomics. The results show that terpene biosynthesis is one of the most crucial secondary metabolic pathways in plants. SH significantly accumulates more terpenes than AC by up regulating the expression of relevant genes. It is worth noting that virus-induced SlHDR silencing not only reduces the expression of downstream genes (SlTPS3, SlFPP, and SlGGPPS) in the terpene biosynthesis pathway, but also significantly affects the synthesis of related terpenoids, there by reducing the insect resistance of tomatoes. The results will be beneficial for understanding the synthesis mechanism of terpenoids in tomatoes and supply new genetic resources for the development of insect-resistant tomatoes.PMID:39998954 | DOI:10.1021/acs.jafc.4c10397
Metabolomic and genomic insights into Micromonospora carbonacea subsp. caeruleus for anti-colorectal compound
Appl Microbiol Biotechnol. 2025 Feb 25;109(1):50. doi: 10.1007/s00253-025-13427-z.ABSTRACTCancer is a predominant contributor to global morbidity and mortality, affecting populations worldwide. Marine Micromonospora species have been identified as significant sources of anticancer compounds. This work aimed to perform a polyphasic approach of isolated strain and conduct comparative metabolomic and genomic analyses to identify compounds with anticancer activity. The study utilized a polyphasic approach on isolated strains for anticancer compound identification. Taxonomic analysis of strain 2MTK254 revealed unique pigment and fatty acid patterns, designating it as a novel Micromonospora carbonacea subsp. caeruleus. Its crude extract displayed significant anti-colorectal activity (66.03% inhibition). Molecular network analysis classified metabolites into eight classes, highlighting a polycyclic tetramate macrolactams (PTMs) compound (P1, C29H38N2O4) with 99.31% inhibitory activity against HCT-116 cell lines (IC50 at 0.125 µM). Genome analysis identified 32 biosynthetic gene clusters (BGCs), including unique PTMs BGCs (83% similarity) linked to the P1 compound. Thus, M. carbonacea subsp. caeruleus 2MTK254 holds promise as a source of novel PTMs with anti-colorectal cancer potential. KEY POINTS: • A novel strain of Micromonospora carbonacea subsp. caeruleus 2MTK254 was isolated in Thailand • A new polycyclic tetramate macrolactam (PTM) with anticancer activity was identified in 2MTK254 • The genome of 2MTK254 has unique secondary metabolite gene clusters.PMID:39998653 | DOI:10.1007/s00253-025-13427-z
Aquirufa esocilacus sp. nov., Aquirufa originis sp. nov., Aquirufa avitistagni, and Aquirufa echingensis sp. nov. discovered in small freshwater habitats in Austria during a citizen science project
Arch Microbiol. 2025 Feb 25;207(4):71. doi: 10.1007/s00203-025-04275-6.ABSTRACTWithin a citizen science project, 112 freshwater habitats in Austria were sampled to get bacterial cultures belonging to the genus Aquirufa using a strategy for targeted isolation. We focused on these bacteria because they are widespread and represent typical freshwater bacteria and, furthermore, the typic red pigmentation facilitates preselection. Among the 113 obtained Aquirufa strains were HETE-83DT, KTFRIE-69FT, OSTEICH-129VT and PLAD-142S6KT, originating from small ponds and a creek. Phylogenetic reconstructions with 16S rRNA gene sequences and genome-based analyses with amino acid sequences of 501 core genes showed that all four strains belonged to the A. antheringensis branch of the genus Aquirufa. Calculation of whole-genome average nucleotide identity values and digital DNA-DNA hybridization values revealed that they represent in each case a new species. The genome sizes of the four strains were between 2.5 and 2.8 Mbp and the G + C values were between 41.4 and 41.8%. Like all type strains of the genus Aquirufa, cells were rod-shaped, and liquid cultures and colonies on agar plates were red-pigmented, likely due to carotenoids. All strains except OSTEICH-129VT showed gliding motility on soft agar plates. All strains grew aerobically but only PLAD-142S6KT could grow weakly under anaerobic conditions. We propose here to establish the names Aquirufa esocilacus sp. nov. for strain HETE-83DT (= DSM 118087T = JCM 37094T), Aquirufa originis sp. nov. for KTFRIE-69FT (= DSM 117798T = JCM 37095T), Aquirufa avitistagni for OSTEICH-129VT (= DSM 118088T = JCM 37100T) and Aquirufa echingensis sp. nov. for PLAD-142S6KT (= DSM 117799T = JCM 37096T).PMID:39998640 | DOI:10.1007/s00203-025-04275-6
Metabolomics and Molecular Networking Approach for Exploring the Effect of Light Intensity and Quality on the Chemical Profile and Accumulation of Glucosinolates in Broccoli Microgreen
J Agric Food Chem. 2025 Feb 25. doi: 10.1021/acs.jafc.4c12826. Online ahead of print.ABSTRACTLight intensity is a crucial factor impacting the cost-efficiency of controlled environment agriculture (CEA). Broccoli microgreens were cultivated under different photosynthetic photon flux densities: 50, 100, and 150 μmol•m-2•s-1 with white light-emitting diodes (LEDs), and an additional far-red (FR) light supplement (20% of total photon flux density) at the 50 μmol•m-2•s-1 intensity. This study examines how low light intensity influences the chemical profile and glucosinolate accumulation in broccoli microgreens through both nontargeted and targeted metabolomics with molecular networking analysis. The analysis identified 28 glucosinolates and 23 phenolic compounds with targeted quantification of 12 glucosinolates. The results showed that FR light supplementation significantly increased the total glucosinolate content compared to white light-only treatments, while similar glucosinolate levels were found across the different white light intensities. These findings provide valuable insights for optimizing LED light intensity to enhance glucosinolate accumulation in broccoli microgreens, thus promoting more efficient energy use in CEA.PMID:39998436 | DOI:10.1021/acs.jafc.4c12826
Metabolic flexibility and reverse remodelling of the failing human heart
Eur Heart J. 2025 Feb 25:ehaf033. doi: 10.1093/eurheartj/ehaf033. Online ahead of print.ABSTRACTBACKGROUND AND AIMS: Cardiac resynchronization therapy (CRT) produces long-term reverse remodelling which requires greater adenosine triphosphate delivery to the contractile machinery. Whilst the heart retains some metabolic flexibility in non-ischaemic cardiomyopathy, whether this correlates with reverse remodelling is unknown. This study investigated whether CRT acutely changes cardiac substrate uptake, and whether this translates to favourable reverse remodelling.METHODS: The effect of CRT on cardiac substrate uptake was assessed via direct coronary flow and arteriovenous measurements, with metabolomic/lipidomic analysis on infusions of insulin/glucose and intralipid. Cardiac function was assessed with left ventricular pressure-volume loops during implantation, and cardiac magnetic resonance before and 6 months following CRT, with and without biventricular pacing.RESULTS: Regardless of substrate infusion, CRT acutely improved stroke work without increasing O2 uptake on both insulin/glucose (by 34%, P = .05) and intralipid (by 36%, P = .03). This was followed by increased fatty acid (FA) uptake on insulin/glucose (R = 0.89, P = .03) and increased β-hydroxybutyrate uptake (R = 0.81, P = .05) during intralipid infusion. After 6 months, there was a 48% (P < .001) reduction in left ventricular end diastolic volume, beyond that achievable by acutely shortening or lengthening QRS duration. Reverse remodelling significantly correlated with increased FA uptake with CRT on insulin/glucose (R = 0.71, P = .05) driven by long and medium chain uptake, and increased ketone uptake with CRT on intralipid (R = 0.79, P = .05).CONCLUSIONS: CRT acutely alters the metabolic phenotype of non-ischaemic cardiomyopathy towards a more physiological picture of FA uptake which correlates with reverse remodelling. Retained metabolic flexibility may therefore be critical for subsequent reverse remodelling.PMID:39998427 | DOI:10.1093/eurheartj/ehaf033
Fission yeast metabolome dynamics during phosphate starvation and replenishment
mBio. 2025 Feb 25:e0024125. doi: 10.1128/mbio.00241-25. Online ahead of print.ABSTRACTInorganic phosphate is an essential nutrient acquired by cells from their environment and assimilated into myriad intracellular metabolites and macromolecules. Here, we characterize the metabolic responses of fission yeast to a 24 h interval of phosphate starvation, during which cells enter a state of G0 quiescence. Time-resolved profiling revealed that many key phosphometabolites were progressively depleted, including (i) NTPs, NDPs, and dNTPs; (ii) coenzyme A, NAD+, NADP+, NADH, and ADP-ribose; (iii) glycolysis pathway intermediates upstream of pyruvate; (iv) pentose phosphate pathway intermediates from 6-phosphogluconate to sedoheptulose-7-phosphate; (v) nucleotide sugars GDP-hexose, UDP-glucose/galactose, and UDP-GalNAc/GlcNAc; and (vi) phospholipid precursors glycerol-3-phosphate, CDP-choline, and glycerophosphocholine. By contrast, early Krebs cycle intermediates accumulated during phosphate starvation. Other metabolic changes included the following: (i) interdiction of de novo pyrimidine synthesis; (ii) depletion of S-adenosylmethionine and S-adenosylhomocysteine; (iii) transient accumulation of polyamine biosynthetic intermediates putrescine and 5-methylthioadenosine; (iv) accumulation of betaine (correlating with an increase in expression of atd1 mRNA encoding aldehyde dehydrogenase); and (v) depletion of aminoadipate pathway intermediates 2-oxoadipate, 2-aminoadipate, and saccharopine. Replenishing phosphate after 24 h of starvation resulted in restoration of the pre-starvation metabolome (over 2 to 12 h) as cells exited quiescence and resumed growth.IMPORTANCE: Fission yeast Schizosaccharomyces pombe is a valuable model system to study cellular phosphate homeostasis and the adaptive responses to chronic phosphate starvation. Previous analyses focused on changes in the fission yeast transcriptome and proteome during phosphate starvation-induced durable G0 quiescence. Here, we deployed metabolomics to survey the scope and temporal order of metabolite changes during 24 h of phosphate starvation and the kinetics of metabolic recovery after cells starved for 24 h are replenished with phosphate. These results contribute to a multi-omics understanding of how phosphate status impacts cell cycle, gene expression, metabolism, and chronological lifespan.PMID:39998228 | DOI:10.1128/mbio.00241-25
Pyruvate kinase directly generates GTP in glycolysis, supporting growth and contributing to guanosine toxicity
mBio. 2025 Feb 25:e0379824. doi: 10.1128/mbio.03798-24. Online ahead of print.ABSTRACTGuanosine triphosphate (GTP) is essential for macromolecular biosynthesis, and its intracellular levels are tightly regulated in bacteria. Loss of the alarmone (p)ppGpp disrupts GTP regulation in Bacillus subtilis, causing cell death in the presence of exogenous guanosine and underscoring the critical importance of GTP homeostasis. To investigate the basis of guanosine toxicity, we performed a genetic selection for spontaneous mutations that suppress this effect, uncovering an unexpected link between GTP synthesis and glycolysis. In particular, we identified suppressor mutations in pyk, which encodes pyruvate kinase, a glycolytic enzyme. Metabolomic analysis revealed that inactivating pyruvate kinase prevents guanosine toxicity by reducing GTP levels. Although traditionally associated with ATP generation via substrate-level phosphorylation, B. subtilis pyruvate kinase in vitro was found to produce GTP and UTP approximately 10 and three times more efficiently than ATP, respectively. This efficient GTP/UTP synthesis extends to Enterococcus faecalis and Listeria monocytogenes, challenging the conventional understanding of pyruvate kinase's primary role in ATP production. These findings support a model in which glycolysis directly contributes to GTP synthesis, fueling energy-demanding processes, such as protein translation. Finally, we observed a synergistic essentiality of the Δndk Δpyk double mutant specifically on glucose, indicating that pyruvate kinase and nucleoside diphosphate kinase are the major contributors to nucleoside triphosphate production and complement each other during glycolysis. Our work highlights the critical role of nucleotide selectivity in pyruvate kinase and its broader implications in cellular physiology.IMPORTANCE: In this study, we reveal that pyruvate kinase, a key glycolytic enzyme, primarily generates GTP from GDP in Bacillus subtilis, relative to other nucleotide triphosphates, such as ATP. This finding, uncovered through genetic selection for mutants that suppress toxic GTP overaccumulation, challenges the conventional understanding that pyruvate kinase predominantly produces ATP via substrate-level phosphorylation. The substantial role of GTP production by pyruvate kinase suggests a model where glycolysis rapidly and directly supplies GTP as the energy currency to power high GTP-demanding processes such as protein synthesis. Our results underscore the importance of nucleotide selectivity (ATP vs GTP vs UTP) in shaping the physiological state and fate of the cell, prompting further exploration into the mechanisms and broader implications of this selective nucleotide synthesis.PMID:39998177 | DOI:10.1128/mbio.03798-24
Metabolomic Profiling of Human Urine Related to Mycotoxin Exposure
Toxins (Basel). 2025 Feb 8;17(2):75. doi: 10.3390/toxins17020075.ABSTRACTHuman exposure to mycotoxins is a global concern since several mycotoxins, such as enniatins and aflatoxins, have shown carcinogenic and neurotoxic effects, and the toxicologic mechanisms of most of them still need to be clarified. This study aims to investigate the metabolic pathways affected by mycotoxin exposure by evaluating metabolite alterations in urine. The participants were 540 women from the Spanish Childhood and Environment Project (INMA). For metabolite identification, a dilute and shoot extraction, followed by HPLC-Q-TOF-MS identification analysis, was performed. Data were processed using Agilent Mass Hunter Workstation with the METLIN database, Agilent Mass Profiler Professional 10.0, and Metaboanalyst 6.0. Over 2000 metabolites were obtained in each sample after feature extraction, and the most significant metabolites (p-value ≤ 0.05, fold change ≥ 2.0) were considered for pathway analysis. Enrichment analysis and topology showed that the most significantly affected pathway was the biosynthesis of unsaturated fatty acids (adjusted p-value = 0.007), with four metabolomic hits associated: linoleic acid, octadecanoic acid/stearic acid, an arachidonic acid metabolite, and (9Z)-octadecenoic acid/oleic acid. Other related pathways (unadjusted p-value ≤ 0.1) included fatty acid biosynthesis, glycerophospholipid metabolism, and ether lipid metabolism. The present study highlights the importance of metabolomics in increasing knowledge of the toxicity mechanisms and health effects of mycotoxins, especially emerging ones.PMID:39998092 | DOI:10.3390/toxins17020075
Integrated Metabolomic and Transcriptomic Analysis Revealed the Mechanism of BHPF Exposure in Endometrium
Toxics. 2025 Jan 27;13(2):100. doi: 10.3390/toxics13020100.ABSTRACTFluorene-9-bisphenol (BHPF) has been increasingly used as a bisphenol A substitute in the synthesis of various products. Previous studies have suggested that BHPF can be released from plastic bottles into drinking water, and BHPF accumulation has been reported to cause various adverse effects in humans. Nevertheless, the impact of BHPF exposure on endometrial epithelial cells remains largely unexplored. Here, we investigated the effects of exposure to different concentrations of BHPF on endometrial cells and used integrated metabolomic and transcriptomic methods to elucidate the underlying molecular mechanisms. Our results revealed significant associations between specific metabolites and genes, indicating that low-concentration exposure to BHPF affects endometrial epithelial cells by targeting pathways related to primary immunodeficiency, in which the key genes are IL7R and PTPRC. High-concentration exposure to BHPF decreased cell viability by regulating the purine metabolism pathway, as well as dysregulating the expression of PGM1, PDE3B, AK9, and ENTPD8. Our study highlights that the health risk of BHPF exposure to endometrial epithelial cells is concentration-dependent and that integrated analysis of metabolomic and transcriptomic data not only revealed the biological effects of BHPF and its underlying mechanisms, but also provided key candidate target genes for further exploration.PMID:39997915 | DOI:10.3390/toxics13020100
The Combined Toxic Effects of Polystyrene Microplastics and Arsenate on Lettuce Under Hydroponic Conditions
Toxics. 2025 Jan 24;13(2):86. doi: 10.3390/toxics13020086.ABSTRACTThe combined pollution of microplastics (MPs) and arsenic (As) has gradually been recognized as a global environmental problem, which calls for detailed investigation of the synergistic toxic effects of MPs and As on plants and their mechanisms. Therefore, the interaction between polystyrene microplastics (PS-MPs) and arsenate (AsO43-) (in the following text, it is abbreviated as As(V)) and its toxic effects on lettuce were investigated in this study. Firstly, chemisorption was identified as the main mechanism between PS-MPs and As(V) by the analysis of adsorption kinetics, adsorption thermodynamics, and Fourier transform infrared spectroscopy (FTIR). At the same time, the addition of As(V) promoted the penetration of PS-MPs through the continuous endodermal region of the Casparis strip. Furthermore, compared with the CK group, it was found that the co-addition of As(V) exacerbated the lowering effect of PS-MPs on the pH value of the rhizosphere environment and the inhibitory effect on root growth. In the P20V10 group, the pH decreased by 33.0%. Compared to the CK group, P20, P20V1, and P20V10 decreased the chlorophyll content by 68.45% (16 SPAD units), 71.37% (17.73 SPAD units), and 61.74% (15.36 SPAD units) and the root length by 19.31% (4.18 cm), 50.72% (10.98 cm), and 47.90% (10.37 cm) in lettuce. P5V10 and P20V10 increased CAT content by 153.54% (33.22 U·(mgprol)-1) and 182.68% ((38.2 U·(mgprol)-1)), Ca by 31.27% and 37.68%, and Zn by 41.85% and 41.85%, but the presence of As(V) reduced Na by 22.85% (P5V1) and 49.95% (P5V10). The co-exposure significantly affected the physiological and biochemical indicators as well as the nutritional quality of the lettuce. Finally, the metabolomic analysis of the lettuce leaves showed that combined pollution with PS-MPs and As(V) affected the metabolic pathways of the tricarboxylic acid cycle (TCA cycle), sulfur metabolism, and pyruvate metabolism. This study provides data for pollution management measures for co-exposure to PS-MPs and As(V).PMID:39997901 | DOI:10.3390/toxics13020086
Matrix Linear Models for Connecting Metabolite Composition to Individual Characteristics
Metabolites. 2025 Feb 19;15(2):140. doi: 10.3390/metabo15020140.ABSTRACTBackground/Objectives: High-throughput metabolomics data provide a detailed molecular window into biological processes. We consider the problem of assessing how association of metabolite levels with individual (sample) characteristics, such as sex or treatment, depend on metabolite characteristics such as pathways. Typically, this is done using a two-step process. In the first step, we assess the association of each metabolite with individual characteristics. In the second step, an enrichment analysis is performed by metabolite characteristics. Methods: We combine the two steps using a bilinear model based on the matrix linear model (MLM) framework previously developed for high-throughput genetic screens. Our method can estimate relationships in metabolites sharing known characteristics, whether categorical (such as type of lipid or pathway) or numerical (such as number of double bonds in triglycerides). Results: We demonstrate the flexibility and interoperability of MLMs by applying them to three metabolomic studies. We show that our approach can separate the contribution of the overlapping triglyceride characteristics, such as the number of double bonds and the number of carbon atoms. Conclusion: The matrix linear model offers a flexible, efficient, and interpretable framework for integrating external information and examining complex relationships in metabolomics data. Our method has been implemented in the open-source Julia package, MatrixLM. Data analysis scripts with example data analyses are also available.PMID:39997765 | DOI:10.3390/metabo15020140
Broussonetia papyrifera Pollen Metabolome Insights, Allergenicity, and Dispersal in Response to Climate Change Variables
Metabolites. 2025 Feb 18;15(2):137. doi: 10.3390/metabo15020137.ABSTRACTBackground/Objectives: Broussonetia papyrifera is a tree-producing allergenic pollen that grows in varied climatic conditions worldwide and causes pollen allergies in susceptible humans. This study aimed to investigate B. papyrifera pollen morphology, pollen metabolome, pollen allergenicity, and climate change's impact on the plant habitat suitability in the future. Methods: Tree pollen was collected in spring from different regions of Pakistan. Pollen samples were subjected to morphological analysis, Fourier transform infrared spectroscopy (FTIR), liquid chromatography-mass spectrometry (LC-MS/MS), and immunoblotting. Results: MaxEnt modeling predicted the tree's future-growth invasion into new regions. Scanning electron microscopy (SEM) and FTIR displayed regional differences in pollen morphology and metabolome correlated to shifts in climatic variables. LC-MS/MS analysis detected four lipids that can potentially stimulate inflammatory responses. Pollen protein immunoblotting studies identified a putative 15 kDa novel allergen and verified previously known 40 kDa, 33 kDa, and 10 kDa allergens. B. papyrifera MaxEnt modeling through ACCESS1.0 and CCSM4 under 2-greenhouse gas emissions scenarios {representative concentration pathway (RCP) 4.5 and 8.5} projected the tree invasion by the years 2050 and 2070. Conclusions: The study findings demonstrate that differences in climatic variables affect B. papyrifera-pollen metabolome and predict the habitat suitability of the tree for invasion in the future. The study results provide a model system for studying other species' pollen morphology, metabolome, future habitat suitability for plant invasion, and associated allergies in response to climate change.PMID:39997762 | DOI:10.3390/metabo15020137
Metabolomic Profiling of the Striatum in Shank3 Knockout ASD Rats: Effects of Early Swimming Regulation
Metabolites. 2025 Feb 16;15(2):134. doi: 10.3390/metabo15020134.ABSTRACTObjectives: This study aimed to investigate the regulatory impact of early swimming intervention on striatal metabolism in Shank3 gene knockout ASD model rats. Methods:Shank3 gene knockout exon 11-21 male 8-day-old SD rats were used as experimental subjects and randomly divided into the following three groups: a Shank3 knockout control group (KC), a wild-type control group (WC) from the same litter, and a Shank3 knockout swimming group (KS). The rats in the exercise group received early swimming intervention for 8 weeks starting at 8 days old. LC-MS metabolism was employed to detect the changes in metabolites in the striatum. Results: There were 17 differential metabolites (14 down-regulated) between the KC and WC groups, 19 differential metabolites (18 up-regulated) between the KS and KC groups, and 22 differential metabolites (18 up-regulated) between the KS and WC groups. Conclusions: The metabolism of striatum in Shank3 knockout ASD model rats is disrupted, involving metabolites related to synaptic morphology, and the Glu and GABAergic synapses are abnormal. Early swimming intervention regulated the striatal metabolome group of the ASD model rats, with differential metabolites primarily related to nerve development, synaptic membrane structure, and synaptic signal transduction.PMID:39997759 | DOI:10.3390/metabo15020134
Metabolomic Insights into Attention Deficit Hyperactivity Disorder: A Scoping Review
Metabolites. 2025 Feb 16;15(2):133. doi: 10.3390/metabo15020133.ABSTRACTBackground /Objectives Attention deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental condition, and symptoms persist into adulthood. Its etiology, though recognized as multifactorial, is still under discussion. Metabolomics helps us to identify pathways associated with functional and structural changes that may be related to symptomatology. This study aimed to characterize potentially altered metabolic pathways and associated biochemical reactions in ADHD. Methods: A scoping review of experimental research was conducted using PubMed, Web of Science, and Scopus using PRISMA ScR. Fifty-five studies were eligible for data extraction, of which fifteen met the criteria for inclusion in the review. Subsequently, the identified metabolites were analyzed in the context of the literature to recognize possible discordant pathways in the disorder. Results: Two groups of relevant neuromodulators of ADHD were found: precursors of monoamines and polyunsaturated fatty acids. The literature was reviewed to discover potential implicated pathways and new metabolites of interest. Conclusions: The study of ADHD biomarkers should focus on measuring precursor, intermediate, and final metabolites of polyunsaturated fatty acids and monoamines in panels or through untargeted analysis to improve the understanding of the pathology and individualization of treatments.PMID:39997758 | DOI:10.3390/metabo15020133
Deep Learning-Based Molecular Fingerprint Prediction for Metabolite Annotation
Metabolites. 2025 Feb 14;15(2):132. doi: 10.3390/metabo15020132.ABSTRACTBackground/Objectives: Liquid chromatography coupled with mass spectrometry (LC-MS) is a commonly used platform for many metabolomics studies. However, metabolite annotation has been a major bottleneck in these studies in part due to the limited publicly available spectral libraries, which consist of tandem mass spectrometry (MS/MS) data acquired from just a fraction of known compounds. Application of deep learning methods is increasingly reported as an alternative to spectral matching due to their ability to map complex relationships between molecular fingerprints and mass spectrometric measurements. The objectives of this study are to investigate deep learning methods for molecular fingerprint based on MS/MS spectra and to rank putative metabolite IDs according to similarity of their known and predicted molecular fingerprints. Methods: We trained three types of deep learning methods to model the relationships between molecular fingerprints and MS/MS spectra. Prior to training, various data processing steps, including scaling, binning, and filtering, were performed on MS/MS spectra obtained from National Institute of Standards and Technology (NIST), MassBank of North America (MoNA), and Human Metabolome Database (HMDB). Furthermore, selection of the most relevant m/z bins and molecular fingerprints was conducted. The trained deep learning models were evaluated on ranking putative metabolite IDs obtained from a compound database for the challenges in Critical Assessment of Small Molecule Identification (CASMI) 2016, CASMI 2017, and CASMI 2022 benchmark datasets. Results: Feature selection methods effectively reduced redundant molecular and spectral features prior to model training. Deep learning methods trained with the truncated features have shown comparable performances against CSI:FingerID on ranking putative metabolite IDs. Conclusion: The results demonstrate a promising potential of deep learning methods for metabolite annotation.PMID:39997757 | DOI:10.3390/metabo15020132
Physiology-Related Variations in the Blood Hormone and Metabolome of Endangered Hog Deer (Axis porcinus)
Metabolites. 2025 Feb 13;15(2):126. doi: 10.3390/metabo15020126.ABSTRACTBackground/Objectives: The hog deer (Axis porcinus) is an endangered species facing significant threats from habitat loss and fragmentation, with only captive populations remaining in China. Expanding breeding programs and restoring wild populations are critical strategies for the species' conservation. Achieving this requires the development of an effective health database and the identification of molecular biomarkers for their physiological traits. Methods: In this study, we present the largest blood metabolomics dataset to date for captive hog deer, comprising 73 healthy individuals. We conducted targeted metabolomics to quantify blood hormone levels and untargeted metabolomics to characterize blood metabolic profiles, aiming to evaluate the associations of sex, age, and weight with metabolic profiles. Results: Our results reveal distinct growth patterns between females and males, with males reaching their body weight plateau at a larger size. We observed significant sex differences (p < 0.05) in blood hormones and metabolic profiles. Females exhibited higher levels of progesterone, hydroxyprogesterone, stress hormones (e.g., cortisol), and proline, while males had higher levels of testosterone, uric acid, phenylalanine, and guanidinosuccinic acid. Notably, body weight emerged as a more important factor than gender in explaining variations in the metabolome, particularly in males. Several blood biomarkers were identified as correlating with age and body weight. Specifically, blood progesterone levels in females were linked to both age and body weight, while in males, uric acid, prolylhydroxyproline, and 3-methylhistidine were associated with these factors. The potential significance of these results for the artificial breeding and conservation of hog deer were discussed. Conclusions: Our study provides a metabolic reference for identifying abnormal individuals and offers potential biomarkers for determining the gender, age, and body weight of hog deer. These findings may have significant implications for the artificial breeding and conservation efforts of the species.PMID:39997752 | DOI:10.3390/metabo15020126
Metabolomics Profiling and Advanced Methodologies for Wheat Stress Research
Metabolites. 2025 Feb 13;15(2):123. doi: 10.3390/metabo15020123.ABSTRACTMetabolomics is an omics technology that studies the types, quantities, and changes of endogenous metabolic substances in organisms affected by abiotic and biotic factors.BACKGROUND/OBJECTIVES: Based on metabolomics, small molecule metabolites in biological organisms can be qualitatively and quantitatively analysed. This method analysis directly correlates with biological phenotypes, facilitating the interpretation of life conditions. Wheat (Triticum aestivum L.) is one of the major food crops in the world, and its quality and yield play important roles in safeguarding food security.METHODS: This review elaborated on the significance of metabolomics research techniques and methods in enhancing wheat resilience against biotic and abiotic stresses.RESULTS: Metabolomics plays an important role in identifying the metabolites in wheat that respond to diverse stresses. The integrated examination of metabolomics with other omics disciplines provides new insights and approaches for exploring resistance genes, understanding the genetic basis of wheat metabolism, and revealing the mechanisms involved in stress responses.CONCLUSIONS: Emerging metabolomics research techniques to propose innovative avenues of research is important to enhance wheat resistance.PMID:39997748 | DOI:10.3390/metabo15020123
Metabolomics Analysis Reveals Characteristic Functional Components in Pigeon Eggs
Metabolites. 2025 Feb 12;15(2):122. doi: 10.3390/metabo15020122.ABSTRACTWe aimed to identify the characteristic functional components of pigeon eggs and the differences among pigeon, chicken, and quail eggs. We analyzed the metabolite profiles of three kinds of eggs using an untargeted metabolomics-based approach to better understand the differences in metabolites among pigeon, chicken, and quail eggs. Then, we quantitatively validated the differences in abundance of partial metabolites through a targeted metabolomics-based approach. A total of 692 metabolites were identified in the three types of eggs. A total of 263 significantly differentially abundant metabolites were found between pigeon eggs and chicken eggs, and 263 significantly differentially abundant metabolites were found between pigeon eggs and quail eggs. The metabolites that were significantly more abundant in pigeon eggs than in other eggs were mainly lipids, lipid-like molecules, nucleosides, nucleotides, and their analogues. We identified the eight metabolites that were significantly greater in abundance in pigeon eggs than in chicken eggs and quail eggs and quantitatively validated the differences in abundance of these metabolites. Our study demonstrates that there are more functional components in pigeon eggs than chicken eggs and quail eggs, especially for the prevention and treatment of various disordered glucose and lipid metabolism-related diseases. The discovery of these differentially abundant metabolites paves the way for further research on the unique nutritional functions of pigeon eggs and the further utilization of pigeon egg products.PMID:39997747 | DOI:10.3390/metabo15020122
Multifluid Metabolomics Identifies Novel Biomarkers for Irritable Bowel Syndrome
Metabolites. 2025 Feb 12;15(2):121. doi: 10.3390/metabo15020121.ABSTRACTBackground/Objectives: Irritable bowel syndrome (IBS) is a complex disorder affecting 10% of the global population, but the underlying mechanisms remain poorly understood. By integrating multifluid metabolomics, we aimed to identify metabolite markers of IBS in a large population-based cohort. Methods: We included individuals from TwinsUK with and without IBS, ascertained using the Rome III criteria, and analysed serum (232 cases, 1707 controls), urine (185 cases, 1341 controls), and stool (186 cases, 1284 controls) metabolites (Metabolon Inc.). Results: After adjusting for covariates, and multiple testing, 44 unique metabolites (25 novel) were associated with IBS, including lipids, amino acids, and xenobiotics. Androsterone sulphate, a sulfated steroid hormone precursor, was associated with lower odds of IBS in both urine (0.69 [95% confidence interval = 0.56-0.85], p = 2.34 × 10-4) and serum (0.75 [0.63-0.90], p = 1.54 × 10-3. Moreover, suberate (C8-DC) was associated with higher odds of IBS in serum (1.36 [1.15-1.61]; p = 1.84 × 10-4) and lower odds of IBS in stool (0.76 [0.63-0.91]; p = 2.30 × 10-3). On the contrary, 32 metabolites appeared to be fluid-specific, including indole, 13-HODE + 9-HODE, pterin, bilirubin (E,Z or Z,Z), and urolithin. The remaining 10 metabolites were associated with IBS in one fluid with suggestive evidence (p < 0.05) in another fluid. Finally, we identified androgenic signalling, dicarboxylates, haemoglobin, and porphyrin metabolism to be significantly over-represented in individuals with IBS compared to controls. Conclusions: Our results highlight the utility of a multi-fluid approach in IBS research, revealing distinct metabolic signatures across biofluids.PMID:39997746 | DOI:10.3390/metabo15020121
Broadly Targeted Metabolomics Analysis of Differential Metabolites Between Bupleurum chinense DC. and Bupleurum scorzonerifolium Willd
Metabolites. 2025 Feb 11;15(2):119. doi: 10.3390/metabo15020119.ABSTRACTBackground/Objectives: Bupleuri Radix is a plant in the Apiaceae family Bupleurum Chinense DC. or Bupleurum scorzonerifolium Willd. root. The dissimilarities in the metabolite profiles of plants directly correlate with the disparities in their clinical efficacy. Methods: Therefore, the wild Bupleurum Chinense DC. (YBC) and wild Bupleurum scorzonerifolium Willd. (YNC) were used as research materials. They were analyzed using the UPLC-MS/MS and the similarities and differences were uncovered based on differential metabolites. Results: Our results proved that the differences in clinical efficacy between YBC and YNC may be attributed to their distinct metabolite profiles, as follows: (1) a total of 12 classes of 2059 metabolites were identified in the roots, with phenolic acids, terpenoids, and flavonoids being the most abundant metabolic products, with 2026 shared components between the two, 2045 in YBC, and 2040 in YNC; (2) a total of 718 differential metabolites were identified, accounting for 35.44% of the shared metabolites. Among them, YBC had 452 metabolites with higher content relative to YNC, representing 62.95%, and 266 components with lower content, representing 37.05%; (3) the KEEG enrichment analysis results show that the differential metabolic pathways are flavone and flavonol biosynthesis, linoleic acid metabolism, arachidonic acid metabolism, sesquiterpenoid and triterpenoid biosynthesis, and linolenic acid metabolism. Conclusions: These new findings will serve as a foundation for further study of the BR biosynthetic pathway and offer insights into the practical use of traditional Chinese medicine in clinical settings.PMID:39997744 | DOI:10.3390/metabo15020119