LuYuxing/MetaBench huggingface dataset:
Question: Write a study description for the study titled 'Limited nutrient availability in the tumor microenvironment renders pancreatic tumors sensitive to allosteric IDH1 inhibitors'.
Answer: Nutrient-deprived conditions in the tumor microenvironment (TME) restrain cancer cell viability due to increased free radicals and reduced energy production. In pancreatic cancer cells, a cytosolic metabolic enzyme, wild-type isocitrate dehydrogenase 1 (wtIDH1), enables the adaptation to these conditions. Under nutrient starvation, wtIDH1 oxidizes isocitrate to generate α-ketoglutarate (αKG) for anaplerosis, and NADPH to support antioxidant defense. In this study, we show that allosteric inhibitors of mutant IDH1 (mIDH1) are potent wtIDH1 inhibitors under conditions present in the TME. We demonstrate that low magnesium levels facilitate allosteric inhibition of wtIDH1, which is lethal to cancer cells when nutrients are limited. Furthermore, the FDA-approved mIDH1 inhibitor ivosidenib (AG-120) dramatically inhibited tumor growth in preclinical models of pancreatic cancer, highlighting this approach as a potential therapeutic strategy against wild-type IDH1 cancers.
Question: Write a study description for the study titled 'LipidOA: A Machine-Learning and Prior-Knowledge-Based Tool for Structural Annotation of Glycerophospholipids'.
Answer: The Paternò-Büchi (PB) reaction is a carbon-carbon double bond (C═C)-specific derivatization reaction that can be used to pinpoint the location(s) of C═C(s) in unsaturated lipids and quantitate the location of isomers when coupled with tandem mass spectrometry (MS/MS). As the data of PB-MS/MS are increasingly generated, the establishment of a corresponding data analysis tool is highly needed. Herein, LipidOA, a machine-learning and prior-knowledge-based data analysis tool, is developed to analyze PB-MS/MS data generated by liquid chromatography-mass spectrometry workflows. LipidOA consists of four key functional modules to realize an annotation of glycerophospholipid (GPL) structures at the fatty acyl-specific C═C location level. These include (1) data preprocessing, (2) picking C═C diagnostic ions, (3) de novo annotation, and (4) result ranking. Importantly, in the result-ranking module, the reliability of structural annotation is sorted via the use of a machine learning classifier and comparison to the total fatty acid database generated from the same sample. LipidOA is trained and validated by four PB-MS/MS data sets acquired using different PB reagents on mass spectrometers of different resolutions and of different biological samples. Overall, LipidOA provides high precision (higher than 0.9) and a wide coverage for structural annotations of GPLs. These results demonstrate that LipidOA can be used as a robust and flexible tool for annotating PB-MS/MS data collected under different experimental conditions using different lipidomic workflows.
Question: Write a study description for the study titled 'Metagenomics and untargeted metabolomics analyses to unravel the formation mechanism of characteristic metabolites in mung bean sour liquid during different fermentation stages'.
Answer: Using LC-MS metabolomics technology, identify the key metabolites during the fermentation of Mung bean sour liquid (MBSL) and analyze their categories. Study the dynamic changes of these metabolites at different fermentation stages, clarify the relationships between the metabolites and the flavor (such as umami taste) and functional properties (such as antioxidant property) of MBSL, and explore the interactions between the microbial communities (such as Lactobacillus and Lactococcus) and the metabolites as well as the regulatory mechanisms of metabolic pathways, so as to provide a theoretical basis for optimizing the production of MBSL, improving product quality, and developing related functional foods.
Question: Write a study description for the study titled 'Untargeted Metabolomics Reveals a Lack Of Synergy between Nifurtimox and Eflornithine against Trypanosoma brucei'.
Answer: A non-targeted metabolomics-based approach is presented that enables the study of pathways in response to drug action with the aim of defining the mode of action of trypanocides. Eflornithine, a polyamine pathway inhibitor, and nifurtimox, whose mode of action involves its metabolic activation, are currently used in combination as first line treatment against stage 2, CNS-involved, human African trypanosomiasis (HAT). Drug action was assessed using an LC-MS based non-targeted metabolomics approach. Eflornithine revealed the expected changes to the polyamine pathway as well as several unexpected changes that point to pathways and metabolites not previously described in bloodstream form trypanosomes, including a lack of arginase activity and N-acetylated ornithine and putrescine. Nifurtimox was shown to be converted to a trinitrile metabolite indicative of metabolic activation, as well as inducing changes in levels of metabolites involved in carbohydrate and nucleotide metabolism. However, eflornithine and nifurtimox failed to synergise anti-trypanosomal activity in vitro, and the metabolomic changes associated with the combination are the sum of those found in each monotherapy with no indication of additional effects. The study reveals how untargeted metabolomics can yield rapid information on drug targets that could be adapted to any pharmacological situation.
Question: Write a study description for the study titled 'Characterisation and localisation of plant metabolites involved in pharmacophagy in the turnip sawfly'.
Answer: Several herbivorous insects consume certain metabolites from plants for other purposes than nutrition, such as defence. Adults of the turnip sawfly, Athalia rosae take up specific terpenoids, called clerodanoids, from Ajuga reptans. These metabolites are slightly modified by the sawflies and influence their mating behaviour and defence against predators. We characterised these metabolites and investigated their localisation in the insect and the specificity of the uptake and metabolite modification. Therefore, we performed feeding assays with adults and larvae of A. rosae as well as larvae of Spodoptera exigua, followed by chemical analyses. Two main clerodanoid-derived metabolites were detected in the abdomen and thorax but also on the surface of the adults. Small amounts were also found in larvae of the sawfly, while they were not detectable in S. exigua. Our findings provide new insights into the peculiarities of pharmacophagy and specialised metabolism in A. rosae.
Question: Write a study description for the study titled 'Metabolic responses of rice cultivars with different tolerance to combined heat and drought stress under field conditions'.
Answer: Rice is susceptible to both heat and drought stress, in particular during flowering and grain filling, when both grain yield and quality may be severely compromised. However, under field conditions, these two stresses rarely occur separately. Under well-watered conditions, plants avoid heat stress by transpirational cooling, while this is not possible under drought conditions. Although investigating combined heat and drought stress is clearly more agronomically relevant than analyzing the effects of the single stresses, only a few studies of this stress combination, in particular under field conditions, have been published. Furthermore, little is known about how plants respond during recovery from drought stress, which also determines plant survival. To address these knowledge gaps, three rice cultivars differing in heat and drought tolerance were grown in the field under control and drought conditions in three consecutive years. Drought was applied either during flowering or during early grain filling, resulting in simultaneous heat stress, leading to reduced grain yield and quality. Analysis by gas chromatography-mass spectrometry (GC-MS) showed distinct metabolic profiles for the three investigated organs (flag leaves, flowering spikelets, developing seeds). The metabolic responses of the plants also strongly differed between cultivars and organs, and between stress and rewatering conditions. Correlation analysis identified potential metabolic markers for grain yield and quality under combined heat and drought stress from stress- and rewatering-regulated metabolites and from metabolites with constitutive differences between the cultivars. These results show that GC-MS can resolve metabolic responses to combined heat and drought stress and subsequent rewatering in different organs of field-grown rice. The metabolite profiles can be used to identify potential marker metabolites for yield stability and grain quality that are expected to improve breeding efforts towards climate change resilient rice.
Question: Write a study description for the study titled 'A high-fiber diet mimics aging-related signatures of caloric restriction in mammals'.
Answer: Caloric restriction (CR) delays aging-related hallmarks in various organisms by slowing growth and development while enhancing metabolic homeostasis. However, desirable diets that harness the metabolic benefits of CR without imposing food intake restrictions remain elusive. Here we evaluated the effects of a high-fiber diet we developed, in which 30% of the macronutrients in a standard diet are replaced with indigestible cellulose, compared to a CR control consisting of a nighttime-2h-restricted feeding regimen. Our findings show that the 2h-restricted feeding triggered a robust systemic response associated with the anti-aging benefits typically observed with CR. Intriguingly, the high-fiber diet did not reduce food intake but mimicked the aging-related signatures of CR in mice from young to old age. These results indicate that the high-fiber diet confers promising benefits for metabolic homeostasis and represents a valuable candidate for further health and aging studies.
Question: Write a study description for the study titled 'Alleviation of Loperamide-Induced Constipation by Lactiplantibacillus plantarum SYS1: Role of Properistaltic Metabolites and Promotion of Enteric Nerve Development via 5-HT4R Activation'.
Answer:  Background: Constipation is a common gastrointestinal disorder. Lactobacillus plantarum has been reported to have the effect of relieving constipation, but its underlying mechanism remains unclear.  Results: Lactiplantibacillus plantarum SYS1 was identified through in vitro probiotic screening and zebrafish models as a potential candidate for alleviating constipation. Further studies confirmed its efficacy in constipated mice, evidenced not only by phenotypic indicators but also by improvements in intestinal villi morphology, expression of gut barrier-related genes and aquaporin genes, and beneficial modulation of gut microbiota structure. Colonic transcriptomics, qPCR, and Western blot results identified the serotonin receptor 4 (5-HT4R) as the likely primary target for SYS1's anti-constipation effect. Subsequent 5-HT4R antagonism experiments confirmed this, as SYS1 lost its efficacy when 5-HT4R was blocked. Further characterization of the enteric nervous structure revealed that SYS1 partially reversed loperamide - induced enteric nervous degeneration, an effect also dependent on 5-HT4R. Experiments in zebrafish and mice showed that the fermented supernatant of SYS1 could alleviate constipation, also primarily targeting 5-HT4R. Non-targeted metabolomics identified maleic acid as a characteristic metabolite of SYS1. Both zebrafish and mouse models demonstrated the anti-constipation effect of maleic acid. This study reveals that L. plantarum SYS1 alleviates constipation by promoting enteric neurogenesis through its metabolite, which activates the 5-HT4R. Conclusions: L. plantarum SYS1 alleviates constipation by promoting enteric neurogenesis through its metabolite, which activates the 5-HT4R pathway. This study elucidates a novel mechanism linking microbial metabolites, and ENS restoration via 5-HT4R signaling.
Question: Write a study description for the study titled 'Public LC-Orbitrap-MS/MS Spectral Library for Metabolite Identification'.
Answer: Liquid chromatography-mass spectrometry (LC-MS)-based untargeted metabolomics studies require high-quality spectral libraries for reliable metabolite identification. We have constructed EMBL-MCF (European Molecular Biology Laboratory-Metabolomics Core Facility), an open LC-MS/MS spectral library that currently contains over 1600 fragmentation spectra from 435 authentic standards of endogenous metabolites and lipids. The unique features of the library include the presence of chromatographic profiles acquired with different LC-MS methods and coverage of different adduct ions. The library covers many biologically important metabolites with some unique metabolites and lipids as compared with other public libraries. The EMBL-MCF spectral library is created and shared using an in-house-developed web application at https://curatr.mcf.embl.de/. The library is freely available online and also integrated with other mass spectral repositories.
Question: Write a study description for the study titled 'Absolute quantitative lipidomics reveals lipidome-wide alterations in aging brain (Mouse brain NEG UPLC-MS assay)'.
Answer: INTRODUCTION: The absolute quantitation of lipids at the lipidome-wide scale is a challenge but plays an important role in the comprehensive study of lipid metabolism. OBJECTIVES: We aim to develop a high-throughput quantitative lipidomics approach to enable the simultaneous identification and absolute quantification of hundreds of lipids in a single experiment. Then, we will systematically characterize lipidome-wide changes in the aging mouse brain and provide a link between aging and disordered lipid homeostasis. METHODS: We created an in-house lipid spectral library, containing 76,361 lipids and 181,300 MS/MS spectra in total, to support accurate lipid identification. Then, we developed a response factor-based approach for the large-scale absolute quantifications of lipids. RESULTS: Using the lipidomics approach, we absolutely quantified 1212 and 864 lipids in human cells and mouse brains, respectively. The quantification accuracy was validated using the traditional approach with a median relative error of 12.6%. We further characterized the lipidome-wide changes in aging mouse brains, and dramatic changes were observed in both glycerophospholipids and sphingolipids. Sphingolipids with longer acyl chains tend to accumulate in aging brains. Membrane-esterified fatty acids demonstrated diverse changes with aging, while most polyunsaturated fatty acids consistently decreased. CONCLUSION: We developed a high-throughput quantitative lipidomics approach and systematically characterized the lipidome-wide changes in aging mouse brains. The results proved a link between aging and disordered lipid homeostasis. Mouse brain NEG UPLC-MS assay data is reported in the current study MTBLS495.Mouse brain POS UPLC-MS assay data associated to this study is reported in MTBLS562.
Question: Write a study description for the study titled 'Antibacterial Monoclonal Antibodies Do Not Disrupt the Intestinal Microbiome or Its Function'.
Answer: Antibiotics revolutionized medicine, however, it is now clear that broad-spectrum antibiotics alter the composition and function of the host’s microbiome. The microbiome plays a key role in human health and its perturbation is increasingly recognized as contributing to many human diseases. Wide spread broad-spectrum antibiotic use has also resulted in the emergence of multi-drug resistant pathogens, spurring development of pathogen-specific strategies such as monoclonal antibodies (mAbs) to combat bacterial infection. Not only are pathogen-specific approaches not expected to induce resistance in non-targeted bacteria, but they are hypothesized to have minimal impact on the gut microbiome. Here, we compare the effects of antibiotics, pathogen-specific mAbs or their controls (saline or c-IgG) on the gut microbiome of 7-week-old, female, C57BL/6 mice. The magnitude of change in taxonomic abundance, bacterial diversity, and bacterial metabolites including short chain fatty acids (SCFA) and bile acids in the fecal pellets from mice treated with pathogen-specific mAbs was no different from animals treated with saline or an IgG control. Conversely, dramatic changes were observed in the relative abundance, as well as alpha- and beta-diversity, of the fecal microbiome, and bacterial metabolites in the feces of all antibiotic-treated mice. Taken together, these results indicate that pathogen-specific mAbs do not alter the fecal microbiome like broad-spectrum antibiotics and may represent a safer, more targeted approach to antibacterial therapy.
Question: Write a study description for the study titled 'Intracellular metabolites from an experimental manipulation of marine microorganisms'.
Answer: The marine environment holds one of the largest pools of reduced organic carbon on Earth. Within this organic carbon are metabolites produced as a result of microbial activity. This project considers the effects of predation and viral lysis on the metabolites found in the surface ocean. Using seawater from the surface ocean, we experimentally manipulated levels of predation and viral lysis. At the beginning and end of the experiment, we sampled the intracellular and extracellular metabolites. The extracts were analyzed using liquid chromatography-based targeted and untargeted metabolomics methods that we have modified for use with marine samples. The untargeted metabolomics data revealed a complex mixture of organic compounds in all of the experimental treatments. However, changes in the majority of the features could not be linked to viral lysis or predation. Within the targeted metabolomics data, increased intracellular levels of osmolytes (glycine betaine, dimethylsulfoniopropionate, proline, and ectoine) were observed under conditions with limited grazing or viral lysis. The molecular insights derived here will explicitly inform our understanding of microbial processes in the surface ocean and the subsequent impacts on the global carbon cycle.
Question: Write a study description for the study titled 'Use of UHPLC-HRMS to profile the metabolites from the serum of breast cancer patients'.
Answer: Breast cancer (BC) is the most common malignancy and the leading cause of cancer-related mortality in women worldwide. As such exploring the metabolic changes during human breast carcinogenesis is important for developing disease prevention methods and treatments. In the present study, non-targeted metabolomics with chemometrics based on ultrahigh performance liquid chromatography-high resolution mass spectrometry was conducted to analyze the differences in serum metabolite patterns between female patients with BC and healthy individuals. A total of 3246 metabolites at various concentrations in the sera of healthy controls and patients with BC were found. Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that arginine, proline, nicotinate, nicotinamide, caffeine and arachidonic acid metabolism as well as fatty acid biosynthesis were significantly altered in BC patients in comparison to controls. These results suggest that serum metabolic profiling has great potential in discovering molecular biomarkers for the detection of BC breast cancer. They may also help to further our understanding of the underlying mechanisms associated with this debilitating disease.
Question: Write a study description for the study titled 'A data integration multi-omics approach to study calorie restriction-induced changes in insulin sensitivity'.
Answer: The mechanisms responsible for weight loss-induced improvement in insulin sensitivity are partially understood. Greater insight can now be achieved through deep phenotyping and data integration. Here, we used an integrative approach to investigate associations between changes in insulin sensitivity and variations in lifestyle factors (diet and physical activity), subcutaneous adipose tissue (sAT) gene expression, metabolomics in serum, urine and feces, and gut microbiota composition after a 6-week calorie restriction period in overweight and obese adults. A spectrum of variables from lifestyle factors, gut microbiota and host multi-omics most associated with insulin sensitivity was identified. These analyses highlight associations between variations in insulin sensitivity, serum branched chain amino acids, sAT genes involved in endoplasmic reticulum stress and ubiquitination, and gut metagenomic species. This work has enhanced previous knowledge on mechanistic links between host glucose homeostasis, lifestyle factors and microbiota, and has identified modifiable factors and biomarkers that may be used to predict and improve individual response to weight loss interventions.
Question: Write a study description for the study titled 'Metabonomics of human fecal extracts characterize ulcerative colitis, Crohn's disease and healthy individuals'.
Answer: This study employs spectroscopy-based metabolic profiling of fecal extracts from healthy subjects and patients with active or inactive ulcerative colitis (UC) and Crohn's disease (CD) to substantiate the potential use of spectroscopy as a non-invasive diagnostic tool and to characterize the fecal metabolome in inflammatory bowel disease (IBD). Stool samples from 113 individuals (UC 48, CD 44, controls 21) were analyzed by 1H nuclear magnetic resonance (NMR) spectroscopy (Bruker 600 MHz, Bruker BioSpin, Rheinstetten, Germany). Data were analyzed with principal component analysis and orthogonal-projection to latent structure-discriminant analysis using SIMCA-P plus 12 and MATLAB. Significant differences were found in the metabolic profiles making it possible to differentiate between active IBD and controls and between UC and CD. The metabolites holding differential power primarily belonged to a range of amino acids, microbiota-related short chain fatty acids, and lactate suggestive of an inflammation-driven malabsorption and dysbiosis of the normal bacterial ecology. However, removal of patients with intestinal surgery and anti-TNF-alpha antibody treatment eliminated the discriminative power regarding UC versus CD. This study consequently demonstrates that 1H NMR spectroscopy of fecal extracts is a potential non-invasive diagnostic tool and able to characterize the inflammation-driven changes in the metabolic profiles related to malabsorption and dysbiosis. Intestinal surgery and medication are to be accounted for in future studies, as it seems to be factors of importance in the discriminative process.