Metabolites最新文献

{"title":"Molecular Mechanism of <i>Cuscuta</i> Haustorium Specialization Inferences from Transcriptome and Metabolome Analysis.","authors":"Xingpan Meng, Ning Lv, Xinglin Wang, Qihang Zhou, Xu Zhang, Ximin Zhang, Zhengdong Zhang, Lunxian Liu, Tie Shen","doi":"10.3390/metabo15030172","DOIUrl":"10.3390/metabo15030172","url":null,"abstract":"<p><strong>Background: </strong><i>Cuscuta australis R. Br.</i> is a parasitic herbaceous plant that obtains nutrients by forming specialized structures called haustoria to invade host plants.</p><p><strong>Methods: </strong>In this study, we elucidated the differences in the gene expression regulation and metabolic characteristics between <i>Cuscuta australis</i> and <i>Glycine max</i> (<i>Glycine max</i> (L.) <i>Merr. Var Williams</i>) through comprehensive transcriptomic and metabolomic analyses.</p><p><strong>Results: </strong>The results demonstrated significant differences in the gene expression and metabolic features between the haustorium and the distal stem segments. The differentially expressed genes absorbed by <i>Cuscuta australis</i> from the soybean host influence amino acid metabolism, and the expression of the S-adenosylmethionine decarboxylase gene may affect the production of 5'-methylthioadenosine. A high expression of the chalcone synthase enzyme could lead to an increased daidzein content. Many <i>Glycine max</i> genes were also integrated into <i>Cuscuta australis</i> within the haustorium.</p><p><strong>Conclusions: </strong>This study systematically analyzed, for the first time, the significant differences in gene expression and metabolic characteristics between the haustoria and distal stem segments of <i>Cuscuta</i>. It also explored the nutrient absorption mechanisms of the host plant. Additionally, the research discovered that <i>Cuscuta</i> can absorb a substantial amount of host genes and adapt to its parasitic lifestyle through differential gene expression and metabolic changes. These findings provide important insights into the parasitic mechanisms of <i>Cuscuta australis</i> and lay the foundation for the development of effective control strategies.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11943614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolomics Approach Revealed Polyunsaturated Fatty Acid Disorders as Pathogenesis for Chronic Pancreatitis-Induced Osteoporosis in Mice.","authors":"Xinlin Liu, Fenglin Hu, Yunshu Zhang, Shurong Ma, Haihua Liu, Dong Shang, Peiyuan Yin","doi":"10.3390/metabo15030173","DOIUrl":"10.3390/metabo15030173","url":null,"abstract":"<p><p><b>Background:</b> Osteoporosis is frequently observed in patients with chronic pancreatitis, and both conditions are closely associated with systemic metabolic disorders. However, the underlying mechanisms linking chronic pancreatitis and osteoporosis remain unclear. <b>Methods:</b> In this study, we utilized high-performance liquid chromatography-mass spectrometry (HPLC-MS) to conduct metabolomics and lipidomics analyses on pancreatic, serum, and other tissues from a mouse model of chronic pancreatitis-induced osteoporosis (CP-OP), with the aim to elucidate the metabolism-related pathogenic mechanisms of CP-OP. <b>Results:</b> We identified over 405 metabolites and 445 lipids, and our findings revealed that several metabolites involving the tricarboxylic acid (TCA) cycle, as well as triacylglycerols and diacylglycerols with higher saturation, were significantly increased in the CP-OP model. In contrast, triglycerides with higher unsaturation were decreased. Differential pathways were enriched in n-3 long-chain polyunsaturated fatty acid metabolism in both pancreatic and bone tissues, and these pathways exhibited positive correlations with bone-related parameters. Furthermore, the modulation of these polyunsaturated fatty acids by Qingyi granules demonstrated significant therapeutic effects on CP-OP, as validated in mouse models. <b>Conclusions:</b> Through the metabolomics approach, we uncovered that disorders in polyunsaturated fatty acids play a critical role in the pathogenesis of CP-OP. This study not only enhances our understanding of the pathogenesis of CP-OP but also highlights the therapeutic potential of targeting polyunsaturated fatty acids as a future intervention strategy for osteoporosis treatment.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Levels of DEFA1, Progranulin, and NRG4 in Patients with Autonomic Neuropathy: Potential Biomarkers for Diagnosis and Prognosis.","authors":"Diana Nikolova, Zdravko Kamenov, Julieta Hristova, Antoaneta Trifonova Gateva","doi":"10.3390/metabo15030169","DOIUrl":"10.3390/metabo15030169","url":null,"abstract":"<p><strong>Background: </strong>Diabetic autonomic neuropathy (DAN) is a severe complication of diabetes that affects the autonomic nervous system, impacting cardiovascular, gastrointestinal, genitourinary, and other systems. This study examines the levels of three potential biomarkers-DEFA1, progranulin, and NRG4-to assess their diagnostic and prognostic value in DAN patients.</p><p><strong>Methods: </strong>This observational, single-center study included 80 patients with type 2 diabetes. Clinical data and laboratory results were collected, and serum levels of DEFA1, progranulin, and NRG4 were measured using ELISA. The presence of DAN was assessed using Ewing's tests. Statistical analyses included <i>t</i>-tests, Pearson's correlations, and ROC analysis to explore associations and the predictive values of the biomarkers.</p><p><strong>Results: </strong>Progranulin levels were significantly elevated in patients with DAN compared to those without (<i>p</i> < 0.05), showing a positive correlation with diabetes duration (r = 0.375; <i>p</i> = 0.01) and a significant predictive value for DAN (AUC = 0.666; <i>p</i> = 0.013). DEFA1 and NRG4 levels did not differ significantly between the groups. Progranulin was also higher in patients who were treated with sulfonylureas and GLP-1 receptor agonists and in those with coronary artery disease.</p><p><strong>Conclusions: </strong>Progranulin emerges as a potential biomarker for the presence and severity of DAN, correlating with disease duration and autonomic dysfunction. While DEFA1 and NRG4 showed no significant association, the findings underscore the importance of further exploring the inflammatory pathways in DAN. Progranulin measurement could enhance early diagnosis and personalized management of autonomic neuropathy in diabetes.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex Differences in Atrial Fibrillation: Evidence from Circulating Metabolites.","authors":"Ningjing Qian, Junyan Jin, Ying Gao, Jiayi Liu, Yaping Wang","doi":"10.3390/metabo15030170","DOIUrl":"10.3390/metabo15030170","url":null,"abstract":"<p><p><b>Background</b>: Significant sex differences exist in atrial fibrillation (AF). Better understanding of its underlying mechanism would help AF management. This study aimed to investigate the contribution of circulating metabolites to sex differences in AF and the association between them. <b>Methods</b>: A total of 108 patients with AF were enrolled. Untargeted metabolomics were performed in plasma samples of male and female patients. Correlation analysis with clinical characteristics and Mendelian randomization were used to identify sex-specific metabolites associated with AF, which was further validated in additional patients. Transcriptomics data of the left atrium were used to investigate the molecular alteration of the left atrium responding to identified sex-specific circulating metabolites. The effect of selected sex-specific metabolites on cardiomyocytes was further investigated. <b>Results</b>: A total of 60 annotated metabolites were found with different levels between male and female patients. Among these sex-specific metabolites, three metabolites, 7-Methylguanosine, succinic acid, and N-Undecylbenzenesulfonic acid, were positively related to the left atrial remodeling. Additionally, succinic acid was significantly associated with increased risk of AF (OR = 1.26; 95% CI: 1.13 to 1.40; <i>p</i> < 0.001). And, SUCLA2, the gene of succinic acid metabolism, was significantly increased in the left atrium of male patients (fold change = 1.53; <i>p</i> = 0.008). Treatment with succinic acid led to cardiomyocyte hypertrophy and mitochondrial dysfunction. <b>Conclusions</b>: This study highlights sex differences in circulating metabolites in patients with AF and identifies the associations between sex-specific metabolites and AF. succinic acid, which is much higher in male patients, contributes to the process of AF.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11943541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association Between Coffee Consumption and Metabolic Syndrome Components Among Saudi Adults.","authors":"Wala I Alzahrani, Sarah N Alsharif, Maryam S Hafiz, Doaa A Alyoubi, Amal M Alrizqi, Raneem A Younes, Alaa M Jahlan, Khaled A Yaghmour","doi":"10.3390/metabo15030163","DOIUrl":"10.3390/metabo15030163","url":null,"abstract":"<p><strong>Background: </strong>Previous research has linked high coffee consumption to an increased risk of metabolic syndrome (MetS). This study aimed to assess the relationship between coffee consumption and MetS components among Saudi adults.</p><p><strong>Methods: </strong>A cross-sectional study was performed on adults who met at least three criteria for a MetS diagnosis. Data concerning demographics, lifestyle, sleeping patterns, medical health, anthropometric measurements, habitual coffee drinking, and lab levels for HDL-C, LDL-C, TC, TGs, HbA1c, and FBG were collected.</p><p><strong>Results: </strong>Of the 95 participants, 51% were women, 75.8% were >50 years old, 75.8% were obese, 62% were used to practicing physical activity, 74.5% never smoked, 56.4% slept < 7 h/day, and 89.5% were coffee consumers. Of these, 94.7% had high waist circumference, 63.2% had high BP, 47.4% had high FBG, 41.1% had low HDL, and 23.2% had high TGs. For coffee consumers, 37.6% drank a small cup, 34.5% drank coffee once daily, 89.4% drank Arabic coffee, and 75.3% added no additives.</p><p><strong>Conclusions: </strong>No significant association was found between coffee consumption patterns and any MetS component, with the exception of elevated TGs, which was strongly associated with coffee cup size and number of daily cups. Waist circumference and BMI had a strong positive correlation with coffee cup size, and there was a significant relationship between the number of daily cups, BMI, and TC. Further prospective studies are needed to establish a causal relationship.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Functions of Major Gut Microbiota in Obesity and Type 2 Diabetes.","authors":"Siman Liu, Zhipeng Tao, Mingyu Qiao, Limin Shi","doi":"10.3390/metabo15030167","DOIUrl":"10.3390/metabo15030167","url":null,"abstract":"<p><p><b>Background:</b> Gut microbiomes play a vital role in maintaining whole-body metabolic homeostasis. It has gained significant attention in recent years due to advancements in genome sequencing technologies and a deeper understanding of its relationship with obesity. However, the specific ways in which different microorganisms directly or indirectly influence host obesity, as well as the underlying mechanisms, remain uncertain because of the complexity of gut microbiota composition. <b>Methods:</b> In this review, we summarize the roles of the major gut microbiota phyla such as <i>Bacteroidetes</i>, <i>Firmicutes</i>, <i>Proteobacteria</i>, and <i>Verrucomicrobia</i> in obesity and type 2 diabetes based on studies published in the past five years on PubMed and Google Scholar. The current therapeutic strategies associated with gut microbiota are also explored from clinical trials, and challenges and future directions are discussed. <b>Results and Conclusions:</b> This review will provide a deeper understanding of the functions of major gut microbiota in obesity and type 2 diabetes, which could lead to more individualized and effective treatments for metabolic diseases.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11943573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Exercise on Arterial Stiffness: Mechanistic Insights into Peripheral, Central, and Systemic Vascular Health in Young Men.","authors":"Yongsheng Lan, Ruisi Wu, Yujuan Feng, Teng Keen Khong, Cunhan Wang, Ashril Yusof, Guangwei Che","doi":"10.3390/metabo15030166","DOIUrl":"10.3390/metabo15030166","url":null,"abstract":"<p><strong>Background/objectives: </strong>Arterial stiffness, a critical predictor of cardiovascular events, varies regionally across peripheral, central, and systemic arteries, necessitating targeted exercise interventions for young men. However, research on the effects of exercise on arterial stiffness in these regions among young men remains limited. This review aims to (i) examine the effects of exercise on arterial stiffness in young men across these regions, and (ii) investigate the underlying mechanisms involved.</p><p><strong>Methods: </strong>Database searches on PubMed, ScienceDirect, Web of Science, and Scopus were conducted up to July 2024. The keywords were: exercise, men/male, and arterial stiffness. Inclusion criteria were studies involving young men, supervised exercise, and arterial stiffness measures. Thirty-five papers were categorized into groups based on peripheral, central and systemic arterial stiffness.</p><p><strong>Results: </strong>Peripheral arterial stiffness: continuous aerobic cycling (light to high intensity), interval aerobic cycling (moderate to high intensity), and 30-s stretching exercises demonstrated positive effects, likely due to short-term changes in sympathetic nervous system activity, nitric oxide availability, and vascular tone. Central arterial stiffness: chronic high-intensity continuous and interval aerobic cycling exercises promoted vascular remodeling, including elastin preservation and collagen regulation. For systemic arterial stiffness, continuous and interval aerobic cycling and light-intensity squats with whole-body vibration exercises improve endothelial function, smooth muscle relaxation, and vascular remodeling.</p><p><strong>Conclusions: </strong>Tailored exercise intervention can effectively reduce arterial stiffness across peripheral, central and systemic regions in young men. Improvements in peripheral stiffness are linked to short-term metabolic shifts, central stiffness responds to long-term remodeling, while systemic arterial stiffness involves both short- and long-term metabolic adaptations.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11943552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disorders of Iron Metabolism: A \"Sharp Edge\" of Deoxynivalenol-Induced Hepatotoxicity.","authors":"Haoyue Guan, Yujing Cui, Zixuan Hua, Youtian Deng, Huidan Deng, Junliang Deng","doi":"10.3390/metabo15030165","DOIUrl":"10.3390/metabo15030165","url":null,"abstract":"<p><strong>Background/objectives: </strong>Deoxynivalenol (DON), known as vomitoxin, is one of the most common mycotoxins produced by <i>Fusarium graminearum</i>, with high detection rates in feed worldwide. Ferroptosis is a novel mode of cell death characterized by lipid peroxidation and the accumulation of reactive oxygen species. Although it has been demonstrated that DON can induce ferroptosis in the liver, the specific mechanisms and pathways are still unknown. The aim of this experiment was to investigate that DON can induce iron metabolism disorders in the livers of mice, thereby triggering ferroptosis and causing toxic damage to the liver.</p><p><strong>Methods: </strong>Male C57 mice were treated with DON at a 5 mg/kg BW concentration as an in vivo model. After sampling, organ coefficient monitoring, liver function test, histopathological analysis, liver Fe²⁺ content test, and oxidative stress-related indexes were performed. The mRNA and protein expression of Nrf2 and its downstream genes were also detected using a series of methods including quantitative real-time PCR, immunofluorescence double-labeling, and Western blotting analysis.</p><p><strong>Results: </strong>DON can cause damage to the liver of a mouse. Specifically, we found that mouse livers in the DON group exhibited pathological damage in cell necrosis, inflammatory infiltration, cytoplasmic vacuolization, elevated relative liver weight, and significant changes in liver function indexes. Meanwhile, the substantial reduction in the levels of glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC) in the DON group indicated that DON also caused oxidative stress in the liver. Notably, DON exposure increased the levels of Fe²⁺ and Malondialdehyde (MDA) in the liver, which provides strong evidence for the occurrence of iron metabolism and ferroptosis disorders. Most importantly, mRNA and protein expression of Nrf2, an important pathway for iron metabolism and ferroptosis, along with its downstream genes, heme oxygenase (HO-1), quinone oxidoreductase (NQO1), glutathione peroxidase (GPX4), and solute carrier gene (SLC7a11), were significantly inhibited in the DON group.</p><p><strong>Conclusions: </strong>Based on our results, the Nrf2 pathway is closely associated with DON-induced iron metabolism disorders and ferroptosis in mouse livers, suggesting that maintaining hepatic iron homeostasis and activating the Nrf2 pathway may be a potential target for mitigating DON hepatotoxicity in the future.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11943501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Studies of <i>Piper auritum</i> Kuntz's Mutagenic and Antimutagenic Properties Using the Ames Test.","authors":"Luis S Muñoz-Carrillo, Eduardo Madrigal-Bujaidar, Sandra L Hernández-Ojeda, José A Morales-González, Eduardo O Madrigal-Santillán, Isela Álvarez-González, J Javier Espinosa-Aguirre","doi":"10.3390/metabo15030164","DOIUrl":"10.3390/metabo15030164","url":null,"abstract":"<p><strong>Background: </strong><i>Piper auritum</i> Kuntz is an endemic plant from Mexico and Central America, where it is called \"hoja santa\", and it is widely used in both local cuisine and traditional medicine. By using the Ames test (strain TA98), we recently demonstrated that ethanol extract from the plant has no mutagenic potential and that it has a significant antimutagenic effect.</p><p><strong>Objectives/methods: </strong>In the present report, we extended this evaluation by using five strains of the <i>Salmonella</i>/microsome mutagenicity assay. Moreover, we evaluated the mutagenic/antimutagenic potential of the major component of the ethanol extract, safrole, with the TA98 strain and employed docking studies to examine the molecular relationship of safrole with the CYP1A1 isoform.</p><p><strong>Results: </strong>Our results confirmed the absence of mutagenicity in the ethanol plant extract, as well as a concentration-dependent inhibitory effect on the damage induced by benzo[a]pyrene (BaP). With respect to safrole, we also determined that the compound has no mutagenic potential and has a strong inhibitory effect on the damage induced by BaP. Docking and kinetic analysis confirmed the coupling of safrole with the active site of the CYP1A1 enzyme, leading to competitive inhibition.</p><p><strong>Conclusions: </strong>These results suggest that the inhibitory effect on the enzyme activity is one of the possible antimutagenic mechanisms.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11943675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting the Pathway Involvement of Compounds Annotated in the Reactome Knowledgebase.","authors":"Erik D Huckvale, Hunter N B Moseley","doi":"10.3390/metabo15030161","DOIUrl":"10.3390/metabo15030161","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Pathway annotations of non-macromolecular (relatively small) biomolecules facilitate biological and biomedical interpretation of metabolomics datasets. However, low pathway annotation levels of detected biomolecules hinder this type of interpretation. Thus, predicting the pathway involvement of detected but unannotated biomolecules has a high potential to improve metabolomics data analysis and omics integration. Past publications have only made use of the Kyoto Encyclopedia of Genes and Genomes-derived datasets to develop machine learning models to predict pathway involvement. However, to our knowledge, the Reactome knowledgebase has not been utilized to develop these types of predictive models. <b>Methods</b>: We created a dataset ready for machine learning using chemical representations of all pathway-annotated compounds available from the Reactome knowledgebase. Next, we trained and evaluated a multilayer perceptron binary classifier using combined metabolite-pathway paired feature vectors engineered from this new dataset. <b>Results</b>: While models trained on a prior corresponding KEGG dataset with 502 pathways scored a mean Matthew's correlation coefficient (MCC) of 0.847 and a 0.0098 standard deviation, the models trained on the Reactome dataset with 3985 pathways demonstrated improved performance with a mean MCC of 0.916, but with a higher standard deviation of 0.0149. <b>Conclusions</b>: These results indicate that the pathways in Reactome can also be effectively predicted, greatly increasing the number of human-defined pathways available for prediction.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}