LuYuxing/MetaBench huggingface dataset:
Question: Write a study description for the study titled 'L-leucine increases the sensitivity of drug-resistant Salmonella to sarafloxacin by stimulating central carbon metabolism and increasing intracellular reactive oxygen species level (LC-MS negative mode)'.
Answer: The overuse of antibiotics has made public health and safety face a serious crisis. It is urgent to develop new clinical treatment methods to combat drug-resistant bacteria to alleviate the health crisis. The efficiency of antibiotics is closely related to the metabolic state of bacteria. However, studies on fluoroquinolone-resistant Salmonella are relatively rare. In this study, non-targeted metabolomics was used to analyze the metabolic difference between sarafloxacin-susceptible Salmonella Typhimurium (SAR-S) and sarafloxacin-resistant Salmonella Typhimurium (SAR-R), and found that the central carbon metabolism was weakened due to drug resistance. We also confirmed that exogenous L-leucine increased the killing effect of sarafloxacin on SAR-R and other clinically resistant Salmonella serotypes. Exogenous L-leucine stimulated the metabolic state of bacteria, especially the TCA cycle, which increased the working efficiency of the electron transfer chain and increased the intracellular NADH, ATP concentration and reactive oxygen species level. Furthermore, we used real-time quantitative PCR to confirm the changes in various metabolic characteristics. Our results suggest that when the metabolism of drug-resistant bacteria is reprogrammed, the bactericidal effect of antibiotics improves. This study further enhances research in the anti-drug resistance field at the metabolic level and provides theoretical support for solving the current problem of sarafloxacin drug resistance, a unique fluoroquinolone drug for animals. To sum up, our research results showed that exogenous L-leucine promotes the bactericidal effect of antibiotics through metabolic modification of drug-resistant bacteria, which has the potential as a new adjuvant of antibiotics.LC-MS negative mode is reported in the current study MTBLS7713.LC-MS positive mode is reported in MTBLS7711.
Question: Write a study description for the study titled 'The Relative Content and Distribution of Absorbed Volatile Organic Compounds in Rats Administered Asari Radix et Rhizoma Are Different between Powder- and Decoction-Treated Groups'.
Answer: Asari Radix et Rhizoma (ARR) is an important traditional Chinese medicine. Volatile organic compounds (VOCs) are the main active constituents of ARR. Research on the metabolite profile of VOCs and the difference of absorbed constituents in vivo after an administration of ARR decoction and powder will be helpful to understand the pharmacological activity and safety of ARR. In this study, headspace solid-phase microextraction gas chromatography mass spectrometry (HS-SPME-GC-MS) was applied to profile the VOCs from ARR in rats in vivo. A total of 153 VOCs were tentatively identified; 101 were original constituents of ARR (98 in the powder-treated group and 43 in the decoction-treated group) and 15 were metabolites, and their metabolic reactions were mainly oxidation and reduction, with only two cases of methylation and esterification, and 37 unclassified compounds were identified only in the ARR-treated group. Of the 153 VOCs identified, 131 were reported in rats after oral administration of ARR for the first time, containing 79 original constituents, 15 metabolites, and 37 unclassified compounds. In the powder-treated group, methyleugenol, safrole, 3,5-dimethoxytoluene (3,5-DMT), 2,3,5-trimethoxytoluene (2,3,5-TMT), and 3,4,5-trimethoxytoluene (3,4,5-TMT) were the main absorbed constituents, the relative contents of which were significantly higher compared to the decoction-treated group, especially methyleugenol, safrole, and 3,5-DMT. In the decoction-treated group, 3,4,5-TMT, 2,3,5-TMT, kakuol, and eugenol were the main constituents with a higher content and wider distribution. The results of this study provide a reference for evaluating the efficacy and safety of ARR.
Question: Write a study description for the study titled 'A Metabonomic Comparison of Human Serum and Plasma Subtypes Using Untargeted NMR Spectroscopy and UPLC-MS (NMR assays)'.
Answer: INTRODUCTION: Differences in the metabolite profiles between serum and plasma are incompletely understood.  OBJECTIVES: To evaluate metabolic profile differences between serum and plasma and among plasma sample subtypes.  METHODS: We analyzed serum, platelet rich plasma (PRP), platelet poor plasma (PPP), and platelet free plasma (PFP), collected from 8 non-fasting apparently healthy women, using untargeted standard 1D and CPMG 1H NMR and reverse phase and hydrophilic (HILIC) UPLC-MS. Differences between metabolic profiles were evaluated using validated principal component and orthogonal partial least squares discriminant analysis.  RESULTS: Explorative analysis showed the main source of variation among samples was due to inter-individual differences with no grouping by sample type. After correcting for inter-individual differences, lipoproteins, lipids in VLDL/LDL, lactate, glutamine, and glucose were found to discriminate serum from plasma in NMR analyses. In UPLC-MS analyses, lysophosphatidylethanolamine (lysoPE)(18:0) and lysophosphatidic acid(20:0) were higher in serum, and phosphatidylcholines (PC)(16:1/18:2, 20:3/18:0, O-20:0/22:4), lysoPC(16:0), PE(O-18:2/20:4), sphingomyelin(18:0/22:0), and linoleic acid were lower. In plasma subtype analyses, isoleucine, leucine, valine, phenylalanine, glutamate, and pyruvate were higher among PRP samples compared with PPP and PFP by NMR while lipids in VLDL/LDL, citrate, and glutamine were lower. By UPLC-MS, PE(18:0/18:2) and PC(P-16:0/20:4) were higher in PRP compared with PFP samples.  CONCLUSIONS: Correction for inter-individual variation was required to detect metabolite differences between serum and plasma. Our results suggest the potential importance of inter-individual effects and sample type on the results from serum and plasma metabolic phenotyping studies.  NMR protocols and data are reported in the current study MTBLS470.  UPLC-MS protocols and data associated to this study are reported in MTBLS465.  Linked Studies: MTBLS465
Question: Write a study description for the study titled 'Large-scale non-targeted serum metabolomics in the Swedish Twin Registry'.
Answer: The TwinGene project, conducted between 2004 and 2008, is a population-based Swedish study of twins born between 1911 and 1958. The study participants have previously participated in a telephone interview called Screening Across the Lifespan Twin Study, conducted between 1998 and 2002. To be included in TwinGene, both twins within a pair had to be alive. In total, 12591 individuals participated by donating blood to the study, and by answering questionnaires about life style and health. For the purpose of metabolomic profiling, we designed a case-cohort of incident coronary heart disease, diabetes, dementia and ischemic stroke events and a matched sub-cohort (controls) stratified on age and sex. In the final analysis we included serum samples from 2,139 individuals.
Question: Write a study description for the study titled 'The genome analysis of Tripterygium wilfordii reveals TwCYP712K1 and TwCYP712K2 responsible for oxidation of friedelin in celastrol biosynthesis pathway'.
Answer: Tripterygium wilfordii is a vine used in Traditional Chinese Medicine (TCM) from the family Celastraceae. The active ingredient celastrol is a friedelane-type pentacyclic triterpenoid, with a putative role as an anti-tumor, immunosuppression, and obesity agent. Here we reported a reference genome assembly of T. wilfordii with high-quality annotation by using a hybrid sequencing strategy, which obtained a 340.12 Mb total genome size, a contig N50 reaching 3.09 Mb, 31593 structure genes, and the repeat percentage was 44.31%. Comparative evolutional analyses showed that T. wilfordii diverged from species of Malpighiales about 102.4 million years ago. In addition, we successfully anchored 91.02% sequences into 23 pseudochromosomes using Hi-C technology and the super-scaffold N50 reached 13.03 Mb. Based on integration of genome, transcriptome and metabolite analyses, as well as in vivo and in vitro enzyme assays of the two CYP450 genes, TwCYP712K1 and TwCYP712K2 the second biosynthesis step of celastrol was investigated and elucidated. Syntenic analysis revealed that TwCYP712K1 and TwCYP712K2 derived from a common ancestor. These results have provided insights into further investigating pathways for celastrol and valuable information to aid the conservation of resources and helped us reveal the evolution of Celastrales.
Question: Write a study description for the study titled 'Metabolomics analysis of the toxic effects of the production of lycopene and its precursors'.
Answer: Using cells as microbial factories enables highly specific production of chemicals with many advantages over chemical syntheses. A number of exciting new applications of this approach are in the area of precision metabolic engineering, which focuses on improving the specificity of target production. In recent work, we have used precision metabolic engineering to design lycopene-producing Escherichia coli for use as a low-cost diagnostic biosensor. To increase precursor availability and thus the rate of lycopene production, we heterologously expressed the mevalonate pathway. We found that simultaneous induction of these pathways increases lycopene production, but induction of the mevalonate pathway before induction of the lycopene pathway decreases both lycopene production and growth rate. Here, we aim to characterize the metabolic changes the cells may be undergoing during expression of either or both of these heterologous pathways. After establishing an improved method for quenching E. coli for metabolomics analysis, we used two-dimensional gas chromatography coupled to mass spectrometry (GCxGC-MS) to characterize the metabolomic profile of our lycopene-producing strains in growth conditions characteristic of our biosensor application. We found that the metabolic impacts of producing low, non-toxic levels of lycopene are of much smaller magnitude than the typical metabolic changes inherent to batch growth. We then used metabolomics to study differences in metabolism caused by the time of mevalonate pathway induction and the presence of the lycopene biosynthesis genes. We found that overnight induction of the mevalonate pathway was toxic to cells, but that the cells could recover if the lycopene pathway was not also heterologously expressed. The two pathways appeared to have an antagonistic metabolic effect that was clearly reflected in the cells' metabolic profiles. The metabolites homocysteine and homoserine exhibited particularly interesting behaviors and may be linked to the growth inhibition seen when the mevalonate pathway is induced overnight, suggesting potential future work that may be useful in engineering increased lycopene biosynthesis.
Question: Write a study description for the study titled 'Prediction and evaluation of the effect of pre-centrifugation sample management on the measurable untargeted LC-MS plasma metabolome'.
Answer: Optimal handling is the most important means to ensure adequate sample quality. We aimed to investigate whether pre-centrifugation delay time and temperature could be accurately predicted and to what extent variability induced by pre-centrifugation management can be adjusted for. We used untargeted liquid chromatography-mass spectrometry (LC-MS) metabolomics to predict and evaluate the influence of pre-centrifugation temperature and delayed time on plasma samples. Pre-centrifugation temperature (4, 25 and 37 °C; classification rate 87%) and time (5–210 min; Q2 = 0.82) were accurately predicted using Random Forest (RF). Metabolites uniquely reflecting temperature and temperature-time interactions were discovered using a combination of RF and generalized linear models. Time-related metabolite profiles suggested a perturbed stability of the metabolome at all temperatures in the investigated time period (5–210 min), and the variation at 4 °C was observed in particular before 90 min. A total of 14 and 8 metabolites were selected and validated for accurate prediction of pre-centrifugation temperature (classification rate 94%) and delay time (Q2 = 0.90), respectively. In summary, the metabolite profile was rapidly affected by pre-centrifugation delay at all temperatures and thus the pre-centrifugation delay should be as short as possible for metabolomics analysis. The metabolite panels provided accurate predictions of pre-centrifugation delay time and temperature in healthy individuals in a separate validation sample. Such predictions could potentially be useful for assessing legacy samples where relevant metadata is lacking. However, validation in larger populations and different phenotypes, including disease states, is needed.
Question: Write a study description for the study titled 'Analysis of fecal microbiome and metabolome changes in goats with pregnant toxemia'.
Answer: Pregnancy toxemia is a common disease, which occurs in older ewes that are pregnant with multiple lambs in the third trimester. Most of the sick goats die within a few days, which can seriously impact the economic benefits of goat breeding enterprises. The disease is believed to be caused by malnutrition, stress and other factors, that lead to the disorder of lipid metabolism, resulting in increased ketone content, ketosis, ketonuria and neurological symptoms. However, the changes in gut microbes and their metabolism in this disease are still unclear. The objective of this experiment was to evaluate the effect of toxemia of pregnancy on the fecal microbiome and metabolomics of ewes. Eight pregnant ewes suspected of having toxemia of pregnancy (PT group) and eight healthy ewes during the same pregnancy (NC group) were selected. Clinical symptoms and pathological changes at necropsy were observed, and liver tissue samples were collected for pathological sections. Jugular venous blood was collected before morning feeding to detect biochemical indexes, and fecal samples were collected simultaneously using 16SrRNA and Liquid Chromatography-Mass Spectrometry (LC-MS) techniques to detect different flora and metabolites. Autopsy revealed that the liver of the pregnancy toxemia goat was enlarged and earthy yellow, and the biochemical results showed that the serum levels of aspartate aminotransferase (AST) and β-hydroxybutyric acid (B-HB) in the PT group were significantly increased, while calcium (Ca) levels were significantly reduced. Sections showed extensive vacuoles in liver tissue sections. The microbiome analysis found that the richness and diversity of the PT microbiota were significantly reduced. Metabolomic analysis showed that 125 differential metabolites were screened in positive ion mode and enriched in 12 metabolic pathways. In negative ion mode, 100 differential metabolites were screened and enriched in 7 metabolic pathways. Evidence has shown that the occurrence of pregnancy toxemia is related to gut microbiota, and further studies are needed to investigate its pathogenesis and provide research basis for future preventive measures of this disease.
Question: Write a study description for the study titled 'Microbial transformation of dietary xenobiotics shapes gut microbiome composition'.
Answer: Diet is a major determinant of gut microbiome composition, and variation in diet-microbiome interactions may contribute to variation in their health consequences. Understanding individual differences requires mechanistic understanding of dietary xenobiotics-microbiome interactions. Here, we map interactions between ~150 small molecule dietary xenobiotics and the gut microbiome, including community composition, compound metabolism, growth inhibitory effects and interindividual variation in these traits. Integrating these measures highlights mechanisms for community remodelling. We identify dietary xenobiotics with growth inhibitory activity and demonstrate how these compounds alter community composition. Microbial metabolism both toxifies and detoxifies these compounds, producing emergent interactions. We identify the gene and enzyme responsible for detoxification of one such dietary xenobiotic, resveratrol, and demonstrate that this enzyme contributes to interindividual variation in community remodelling. Together, these results systematically map interactions between dietary xenobiotics and the gut microbiome and suggest how toxification and detoxification contributes to interpersonal differences in microbiome response to diet.
Question: Write a study description for the study titled 'Metabolic network construction reveals probiotic-specific colonization resistance in a synthetic small intestinal community'.
Answer: The gut microbiota is essential to host health. Probiotics can be used as a microbiota targeted therapy to improve host health. However, probiotic molecular mechanisms of action and probiotics targeting the small intestinal microbiota are often not elucidated. In this study, we construct a three species synthetic community resembling the upper small intestine. We show that probiotic supplementation results in direct colonization resistance by affecting the metabolism of the community in a probiotic specific manner. Supplementation with Streptococcus thermophilus increased lactate production and reduced the pH, but did not affect the overall metabolic network substantially. In contrast, Lactobacillus casei did not alter lactate production or the pH, but increased the resistance to perturbations and nutrient utilization. Furthermore, supplementation of L. casei together with kynurenine increased metabolism along the kynurenine pathway and resulted in an elevated concentration of kynurenic acid, possibly leading to indirect colonization resistance. Together, we show how network construction can be used to improve the current or identify novel microbiota-targeted therapies.
Question: Write a study description for the study titled 'Dynamic partitioning of branched-chain amino acids-derived nitrogen supports renal cancer progression'.
Answer: Metabolic reprogramming is critical for tumor initiation and progression. However, the exact impact of specific metabolic changes on cancer progression is poorly understood. Here, we integrate multimodal analyses of primary and metastatic clonally-related clear cell renal cancer cells (ccRCC) grown in physiological media to identify key stage-specific metabolic vulnerabilities. We show that a VHL loss-dependent reprogramming of branched-chain amino acid catabolism sustains the de novo biosynthesis of aspartate and arginine enabling tumor cells with the flexibility of partitioning the nitrogen of the amino acids depending on their needs. Importantly, we identify the epigenetic reactivation of argininosuccinate synthase (ASS1), a urea cycle enzyme suppressed in primary ccRCC, as a crucial event for metastatic renal cancer cells to acquire the capability to generate arginine, invade in vitro and metastasize in vivo. Overall, our study uncovers a novel mechanism of metabolic flexibility occurring during ccRCC progression, paving the way for the development of novel stage-specific therapies
Question: Write a study description for the study titled 'PROMIS, global analysis of PROtein-Metabolite Interactions using Size separation in Arabidopsis thaliana'.
Answer: Small molecules not only represent cellular building blocks and metabolic intermediates, but also regulatory ligands and signaling molecules that interact with proteins. Although these interactions affect cellular metabolism, growth, and development, they have been largely understudied. Herein, we describe a method, dubbed PROtein-Metabolite Interactions using Size separation (PROMIS) that allows simultaneous, global analysis of endogenous protein-small molecule and of protein‒protein complexes. To this end, a cell-free native lysate from Arabidopsis thaliana cell cultures was fractionated by size-exclusion chromatography, followed by quantitative metabolomic and proteomic analyses. Proteins and small molecules showing similar elution behavior, across protein containing fractions, constituted putative interactors. Applying PROMIS to an A. thaliana extract, we ascertained known protein‒protein (PPIs) and protein-metabolite (PMIs) interactions and reproduced binding between small-molecule protease inhibitors and their respective proteases. More importantly, we present examples of two experimental strategies that exploit the PROMIS dataset to identify novel PMIs. By looking for similar elution behavior of metabolites and enzymes belonging to the same biochemical pathways, we identified putative feedback and feed-forward regulations in pantothenate biosynthesis and the methionine salvage cycle, respectively. By combining PROMIS with an orthogonal affinity purification approach, we identified an interaction between the dipeptide Tyr-Asp and the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase. In summary, we present proof of concept for a powerful experimental tool that enables system-wide analysis of PMIs and PPIs across all biological systems. The dataset obtained here comprises nearly 140 metabolites and 5000 proteins, which can be mined for putative interactors.
Question: Write a study description for the study titled 'Operational tolerance after hematopoietic stem cell transplantation is characterized by distinct transcriptional, phenotypic, and metabolic signatures (Cohort 2).'.
Answer: The mechanisms underlying operational tolerance after hematopoietic stem cell transplantation in humans are poorly understood. We studied two independent cohorts of patients who underwent allogeneic hematopoietic stem cell transplantation from human leukocyte antigen-identical siblings. Primary tolerance was associated with long-lasting reshaping of the recipients' immune system compared to their healthy donors with an increased proportion of regulatory T cell subsets and decreased T cell activation, proliferation, and migration. Transcriptomics profiles also identified a role for nicotinamide adenine dinucleotide biosynthesis in the regulation of immune cell functions. We then compared individuals with operational tolerance and nontolerant recipients at the phenotypic, transcriptomic, and metabolomic level. We observed alterations centered on CD38+-activated T and B cells in nontolerant patients. In tolerant patients, cell subsets with regulatory functions were prominent. RNA sequencing analyses highlighted modifications in the tolerant patients' transcriptomic profiles, particularly with overexpression of the ectoenzyme NT5E (encoding CD73), which could counterbalance CD38 enzymatic functions by producing adenosine. Further, metabolomic analyses suggested a central role of androgens in establishing operational tolerance. These data were confirmed using an integrative approach to evaluating the immune landscape associated with operational tolerance. Thus, balance between a CD38-activated immune state and CD73-related production of adenosine may be a key regulator of operational tolerance.
Question: Write a study description for the study titled 'Metabolomics of sebum reveals lipid dysregulation in Parkinson's disease'.
Answer: Parkinson's disease (PD) is a progressive neurodegenerative disorder, which is characterised by degeneration of distinct neuronal populations, including dopaminergic neurons of the substantia nigra. Here, we use a metabolomics profiling approach to identify changes to lipids in PD observed in sebum, a non-invasively available biofluid. We used liquid chromatography-mass spectrometry (LC-MS) to analyse 274 samples from participants (80 drug naïve PD, 138 medicated PD and 56 well matched control subjects) and detected metabolites that could predict PD phenotype. Pathway enrichment analysis shows alterations in lipid metabolism related to the carnitine shuttle, sphingolipid metabolism, arachidonic acid metabolism and fatty acid biosynthesis. This study shows sebum can be used to identify potential biomarkers for PD.