LuYuxing/MetaBench huggingface dataset:
Question: Write a study description for the study titled 'Wolbachia modulation of lipid metabolism in Aedes albopictus mosquito cells'.
Answer: Certain strains of the intracellular endosymbiont Wolbachia can strongly inhibit or block the transmission of viruses such as dengue by Aedes mosquitoes, and the mechanisms responsible are still not well understood. Direct infusion and liquid chromatography FT-ICR mass spectrometry based lipidomicse DIMS and LCMS analyses were conducted using Aedes albopictus Aa23 cells that were infected with the wMel and wMelPop strains of Wolbachia compared to uninfected cells. Substantial shifts in the cellular lipid profile were apparent in the presence of Wolbachia. Most significantly, sphingolipids were depleted across all classes, and some reduction in diacylglyerol fatty acids and phosphatidylcholines was also observed. These lipid classes have previously been shown to be selectively enriched in DENV-infected mosquito cells, suggesting that Wolbachia may produce a cellular lipid environment that is antagonistic to viral replication. The data improve understanding of the intracellular interactions between Wolbachia and mosquitoes.
Question: Write a study description for the study titled 'A multiomic approach to reveal gastrointestinal toxicity mechanisms associated with mycophenolate mofetil in neuromyelitis optica spectrum disorders'.
Answer: Mycophenolate mofetil (MMF) has been widely prescribed for neuromyelitis optica spectrum disorders (NMOSD) although some patients experience severe gastrointestinal (GI) side effects following MMF administration. Our study investigated the potential mechanisms of this toxicity in NMOSD patients. We constructed MMF-induced colitis mouse model and produced a multi-omic dataset in which microbiome and metabolome analysis from the mouse GI tract to decipher the mechanisms of MMF GI toxicity. Further, 17 female NMOSD patients treated with MMF were prospectively enrolled and grouped according to the diarrhea symptom as non-diarrhea NMOSD group (NM) and diarrhea NMOSD group (DNM) as well as healthy controls (HC, 12 female). The gut microbiota was analyzed using 16S rRNA sequencing of stool samples. In the mouse model, we found that vancomycin administration drastically altered the colon content metabolomes and microbiomes and prevented MMF-induced body weight loss, cecal and colon tissue injury. Bacteroidetes and Firmicutes converted phenyl-beta-D-glucuronide (MPAG) to mycophenolic acid (MPA) that could result in damaged intestinal tissue. We also demonstrated that the alpha diversity in the DNM group was increased and this was accompanied by increased Firmicutes and Proteobacteria abundance. Collectively, these results reveal that alterations of the gut microbiome and metabolome contribute to MMF-induced colitis. Modifying of the gut microbiome and metabolome may alleviate MMF-induced GI toxicity in NMOSD patients.
Question: Write a study description for the study titled 'Tetrandrine regulates NAADP-mediated calcium signalling 1 through a novel LIMP-2-dependent, sphingosine-mediated mechanism.'.
Answer: Tetrandrine (Tet) is an highly potent inhibitor of Ebola virus replication by blocking NAADP51 dependent calcium release through endolysosomal two-pore channels (TPCs) and a moderately potent anti-tumor agent. Using a clickable, photoaffinity probe of Tet, we identified lysosomal integral membrane protein-2 (LIMP-2) as the genuine molecular target of Tet and a novel regulator for NAADP-dependent calcium release. Tet binds to the ectodomain of LIMP-2 and inhibits its cholesterol and sphingosine transport function, resulting in the alteration of cellular lipid profiles and metabolic pathways, and development of acute hypercholesterolemia and hepatosteatosis in mice. Cells treated with Tet or depleted for LIMP-2 similarly inhibits NAADP-dependent calcium release, which can be restored by eliminating lysosomal cholesterol and sphingosines. Importantly, addition of sphingosine dose-dependently tiggers lysosomal calcium release through TPCs, and restores NAADP-dependent calcium release in Tet-treated or LIMP-2-depleted cells. At higher concentrations, Tet induced apoptosis associated with unfolded protein response activation in a LIMP-2-independent manner. We identified Tet as the first known inhibitor of LIMP-2, discerned its pharmacological principle in regulating calcium signalling and cell death, and discovered a novel LIMP-2-regulated, sphingosine-dependent lysosomal calcium signalling pathway. Our findings have profound implications in the development of Tet and LIMP-2 inhibitors into clinical therapeutics.
Question: Write a study description for the study titled 'Non-invasive urinary metabolomic profiles discriminate biliary atresia from infantile hepatitis syndrome'.
Answer: INTRODUCTION: Neonatal cholestatic disorders are a group of hepatobiliary diseases occurring in the first 3 months of life. The most common causes of neonatal cholestasis are infantile hepatitis syndrome (IHS) and biliary atresia (BA). The clinical manifestations of the two diseases are too similar to distinguish them. However, early detection is very important in improving the clinical outcome of BA. Currently, a liver biopsy is the only proven and effective method used to differentially diagnose these two similar diseases in the clinic. However, this method is invasive. Therefore, sensitive and non-invasive biomarkers are needed to effectively differentiate between BA and IHS. We hypothesized that urinary metabolomics can produce unique metabolite profiles for BA and IHS.OBJECTIVES: The aim of this study was to characterize urinary metabolomic profiles in infants with BA and IHS, and to identify differences among infants with BA, IHS, and normal controls (NC).METHODS: Urine samples along with patient characteristics were obtained from 25 BA, 38 IHS, and 38 NC infants. A non-targeted gas chromatography-mass spectrometry (GC-MS) metabolomics method was used in conjunction with orthogonal partial least squares discriminant analysis (OPLS-DA) to explore the metabolomic profiles of BA, IHS, and NC infants.RESULTS: In total, 41 differentially expressed metabolites between BA vs. NC, IHS vs. NC, and BA vs. IHS were identified. N-acetyl-D-mannosamine and alpha-aminoadipic acid were found to be highly accurate at distinguishing between BA and IHS.CONCLUSIONS: BA and IHS infants have specific urinary metabolomic profiles. The results of our study underscore the clinical potential of metabolomic profiling to uncover metabolic changes that could be used to discriminate BA from IHS.
Question: Write a study description for the study titled 'Metabolite annotation of rat epididymis with High-resolution imaging mass spectrometry'.
Answer: Infertility or subfertility is a widespread problem with approximately 25% of couples seeking medical help. For about half the cases it lies in the male partner. Male infertility is caused by problems that affect sperm production, maturation and/or transport. In this study the role played by the epididymis in the post-testicular maturation of spermatozoa during its transit through this organ was investigated using FT-ICR imaging mass spectrometry of metabolites and the FDR-controlled metabolite annotation platform MetaSpace for high-resolution imaging mass spectrometry. This study together with MTBLS313 provides the accompanying data for FDR-controlled metabolite annotation for high-resolution imaging mass spectrometry.
Question: Write a study description for the study titled 'Does Storage Post Sampling Influence the Stability of Sebum when used for Mass Spectrometry Metabolomics Analysis?'.
Answer: Sebum is a biofluid excreted by sebaceous glands in the skin. In recent years sebum has been shown to contain endogenous metabolites diagnostic of disease, with remarkable results for Parkinson’s Disease. Given that sebum sampling is facile and non-invasive, its potential for use in clinical biochemistry diagnostic assays should be explored including the parameters for standard operating procedures around collection, transport and storage. To this aim we have here investigated the reproducibility of mass spectrometry data from sebum in relation to both storage temperature and length of storage. Sebum samples were collected from volunteers and stored for up to 4 weeks at a range of temperatures: ambient (circa 17 °C), -20 °C and -80 °C. Established extraction protocols were employed and the samples were analysed by two chromatographic mass spectrometry techniques and data investigated using PCA, PLS-DA and ANOVA. We cannot discriminate samples as a function of storage temperature or time stored in unsupervised analysis using data acquired via TD-GC-MS and LC-IM-MS, although the sampling of volatiles was susceptible to batch effects. This study indicates that the requirements for storage and transport of sebum samples that may be used in clinical assays are far less stringent than for liquid samples and indicate that sebum is suitable for remote and at home sampling prior to analysis.
Question: Write a study description for the study titled 'Airway Dysbiosis Accelerates Lung Function Decline in Chronic Obstructive Pulmonary Disease (Murine UPLC-MS/MS assays)'.
Answer: Progressive lung function decline is a hallmark of chronic obstructive pulmonary disease (COPD). Airway dysbiosis occurs in COPD, but whether it contributes to disease progression remains unknown. Here we showed, through a longitudinal analysis on two cohorts involving four UK centers, that baseline airway dysbiosis in COPD patients, characterized by enrichment of opportunistic pathogenic taxa, was associated with rapid forced expiratory volume in one second (FEV1) decline over two years. The dysbiosis was associated with exacerbation-related FEV1 fall and sudden FEV1 fall at stability, contributing to long-term FEV1 decline. The microbiota- FEV1-decline association was validated in a third cohort in China. Human multi-omics and murine studies showed that airway Staphylococcus aureus colonization promoted lung function decline through homocysteine, which elicited a neutrophil apoptosis-to-NETosis shift via AKT1-S100A8/A9 axis. S. aureus depletion via bacteriophages restored lung function in emphysema mice, providing a fresh approach to slow COPD progression by targeting airway microbiome.Linked studies:UPLC-MS/MS assays of murine samples are reported in this study.UPLC-MS/MS assays of human samples are reported in MTBLS5423.UPLC-MS/MS assays of original cohort human samples are reported in MTBLS4017.
Question: Write a study description for the study titled 'Metabolomics biomarkers of hepatocellular carcinoma in a prospective cohort of patients with cirrhosis'.
Answer: BACKGROUND & AIMS: The effectiveness of surveillance for hepatocellular carcinoma (HCC) in patients with cirrhosis is limited, due to inadequate risk stratification and suboptimal performance of current screening modalities.METHODS: We developed a multicenter prospective cohort of patients with cirrhosis undergoing surveillance with MRI and applied global untargeted metabolomics to 612 longitudinal serum samples from 203 patients. Among them, 37 developed HCC during follow-up.RESULTS: We identified 150 metabolites with significant abundance changes in samples collected prior to HCC (Cases) compared to samples from patients who did not develop HCC (Controls). Tauro-conjugated bile acids and gamma-glutamyl amino acids were increased, while acyl-cholines and deoxycholate derivatives were decreased. Seven amino acids including serine and alanine had strong associations with HCC risk, while strong protective effects were observed for N-acetylglycine and glycerophosphorylcholine. Machine learning using the 150 metabolites, age, gender, and PNPLA3 and TMS6SF2 single nucleotide polymorphisms, identified 15 variables giving optimal performance. Among them, N-acetylglycine had the highest AUC in discriminating Cases and Controls. When restricting Cases to samples collected within 1 year prior to HCC (Cases-12M), additional metabolites including microbiota-derived metabolites were identified. The combination of the top six variables identified by machine learning (alpha-fetoprotein, 6-bromotryptophan, N-acetylglycine, salicyluric glucuronide, testosterone sulfate and age) had good performance in discriminating Cases-12M from Controls (AUC 0.88, 95% CI 0.83-0.93). Finally, 23 metabolites distinguished Cases with LI-RADS-3 lesions from Controls with LI-RADS-3 lesions, with reduced abundance of acyl-cholines and glycerophosphorylcholine-related lysophospholipids in Cases.CONCLUSIONS: This study identified N-acetylglycine, amino acids, bile acids and choline-derived metabolites as biomarkers of HCC risk, and microbiota-derived metabolites as contributors to HCC development.
Question: Write a study description for the study titled 'Deletion of glycerol channel aquaporin-9 (Aqp9) impairs long-term blood glucose control in C57BL/6 leptin receptor-deficient (db/db) obese mice'.
Answer: Deletion of the glycerol channel aquaporin-9 (Aqp9) reduces postprandial blood glucose levels in leptin receptor deficient (db/db) obese mice on a C57BL/6×C57BLKS mixed genetic background. Furthermore, shRNA mediated reduction of Aqp9 expression reduces liver triacylglycerol (TAG) accumulation in a diet induced rat model of obesity. The aim of this study was to investigate metabolic effects of Aqp9 deletion in coisogenic db/db mice of the C57BL/6 background. Aqp9wt db/db and Aqp9-/- db/db mice did not differ in body weight and liver TAG contents. On the C57BL/6 genetic background we observed elevated plasma glucose in Aqp9-/- db/db mice (+ 1.1 mM, life-time average) while plasma insulin concentration was reduced at time of death. Glucose levels changed similarly in pentobarbital anesthetized, glucagon challenged Aqp9wt db/db and Aqp9-/- db/db mice. Liver transcriptional profiling did not detect differential gene expression between genotypes. Metabolite profiling revealed a sex independent increase in plasma glycerol (+55%), glucose (+24%) and reduction in threonate (all at q<0.1) in Aqp9-/- db/db mice compared to controls. Metabolite profiling thus confirms a role of AQP9 in glycerol metabolism of obese C57BL/6 db/db mice. In this animal model of obesity Aqp9 gene deletion elevates plasma glucose and does not alleviate hepatosteatosis.
Question: Write a study description for the study titled 'Physiological and Metabolic Responses of Zymomonas mobilis to Lignocellulosic Hydrolysate'.
Answer: This study provides a systems-level evaluation of how Zymomonas mobilis responds to hydrolysate stress, revealing distinct physiological and lipid membrane remodeling responses.
Question: Write a study description for the study titled 'Mass spectrometry data of metabolomics analysis of Nepenthes pitchers'.
Answer: Hybridisation plays a significant role in the evolution and diversification of plants. Hybridisation among Nepenthes species is extensive, either naturally or man-made. To investigate the effects of hybridisation on the chemical compositions, we carried out metabolomics study on pitcher tissue of Nepenthes ampullaria, Nepenthes rafflesiana and their hybrid, Nepenthes × hookeriana. Pitcher samples were harvested and extracted in methanol:chloroform:water via sonication-assisted extraction before analysed using LC-TOF-MS. MS data were analysed using XCMS online version 2.2.5. This is the first MS data report towards the profiling, identification and comprehensive comparison of metabolites present in Nepenthes species.
Question: Write a study description for the study titled 'Metabolomic Analysis of Fission Yeast at the Onset of Nitrogen Starvation'.
Answer: Microorganisms naturally respond to changes in nutritional conditions by adjusting their morphology and physiology. The cellular response of the fission yeast S. pombe to nitrogen starvation has been extensively studied. Here, we report time course metabolomic analysis during one hour immediately after nitrogen starvation, prior to any visible changes in cell morphology except for a tiny increase of cell length per division cycle. We semi-quantitatively measured 75 distinct metabolites, 60% of which changed their level over 2-fold. The most significant changes occurred during the first 15 min, when trehalose, 2-oxoglutarate, and succinate increased, while purine biosynthesis intermediates rapidly diminished. At 30–60 min, free amino acids decreased, although several modified amino acids—including hercynylcysteine sulfoxide, a precursor to ergothioneine—accumulated. Most high-energy metabolites such as ATP, S-adenosyl-methionine or NAD+ remained stable during the whole time course. Very rapid metabolic changes such as the shut-off of purine biosynthesis and the rise of 2-oxoglutarate and succinate can be explained by the depletion of NH4Cl. The changes in the levels of key metabolites, particularly 2-oxoglutarate, might represent an important mechanistic step to trigger subsequent cellular regulations.
Question: Write a study description for the study titled 'Metabolic alterations caused by the mutation and overexpression of the Tmem135 gene'.
Answer: Mitochondria are highly dynamic organelles undergoing fusion, fission and degradation. Although mitochondria are known to be essential for cellular metabolism, it is not fully understood how mitochondrial dynamics affect cellular metabolism. We previously identified a mouse gene, transmembrane protein 135 (TMEM135) that plays a role in the regulation of mitochondrial dynamics. Mice with mutant Tmem135 (Tmem135FUN025/FUN025) show accelerated aging phenotypes and age-related pathologies in the retina including the retinal pigment epithelium (RPE). We also generated a transgenic mouse line globally overexpressing the Tmem135 gene (Tmem135 TG). In several tissues and cells that we studied such as the retina, heart and fibroblast cells, we observed that the Tmem135 mutation causes elongated mitochondria, while over-expression of Tmem135 results in fragmented mitochondria. These unique mouse models allow us to test how abnormal mitochondrial dynamics affect metabolic signatures of tissues and cells. In this study, we identified metabolic changes in primary RPE cell cultures as well as tissues isolated from Tmem135FUN025/FUN025 mice (fusion > fission) and Tmem135 TG mice (fusion < fission) using nuclear magnetic resonance (NMR) spectroscopy. Metabolomics analysis revealed a tissue-dependent response to alterations to Tmem135 whereby, significant metabolic changes were observed in heart in both mutant and TG mice as compared to WT while negligible effects were observed in cerebellum and hippocampus. We also observed changes in Tmem135FUN025/FUN025 and Tmem135 TG RPE cells associated with osmosis, glucose metabolism and phospholipid metabolism. Significant depletion of NAD+ was detected in both Tmem135FUN025/FUN025 and Tmem135 TG RPE cells, indicating that imbalance in mitochondrial dynamics to both directions lowers the cellular NAD+ level. Thus, we have identified metabolomic changes associated with imbalanced mitochondrial dynamics in heart tissue and RPE cells which can likely lead to functional abnormalities.
Question: Write a study description for the study titled 'High-Precision Automated Workflow for Urinary Untargeted Metabolomic Epidemiology'.
Answer: Urine is a non-invasive biofluid that is rich in polar metabolites and well-suited for metabolomic epidemiology. However, due to individual variability in health and hydration status, the physiological concentration of urine can differ >15-fold, which can pose major challenges in untargeted LC-MS metabolomics. Although numerous urine normalization methods have been implemented (e.g., creatinine, specific gravity – SG), most are manual and therefore not practical for population-based studies. To address this issue, we developed a method to measure SG in 96-well-plates using a refractive index detector (RID), which exhibited accuracy within 85-115% and 540 urinary metabolites including endogenous and exogenous compounds. This platform is suitable for performing urinary untargeted metabolomic epidemiology and will be useful for applications in population-based molecular phenotyping.
Question: Write a study description for the study titled 'Unknown Metabolite Annotation in Mouse Aging using Ion Mobility Collision Cross-Section Atlas (AllCCS)'.
Answer: The metabolome includes not just known but also unknown metabolites; however, metabolite annotation remains the bottleneck in untargeted metabolomics. Ion mobility – mass spectrometry (IM-MS) has emerged as a promising technology by providing multi-dimensional characterizations of metabolites. Here, we curated an ion mobility CCS atlas, namely AllCCS, and developed an integrated strategy for metabolite annotation using known or unknown chemical structures. The AllCCS atlas covers vast chemical structures with >5000 experimental CCS records and ~12 million calculated CCS values for >1.6 million small molecules. We demonstrated the high accuracy and wide applicability of AllCCS with medium relative errors of 0.5-2% for a broad spectrum of small molecules. AllCCS combined with in-silico MS/MS spectra facilitated multi-dimensional match and substantially improved the accuracy and coverage of both known and unknown metabolite annotation from biological samples. Together, AllCCS is a versatile resource that enables confident metabolite annotation, revealing comprehensive chemical and metabolic insights towards biological processes.Unknown Metabolite Annotation in Mouse Aging assay is reported in the current study MTBLS1622.Known Metabolite Annotation in Different Biological Samples assays are reported in MTBLS1693.
Question: Write a study description for the study titled 'Metabolomics identifies the intersection of phosphoethanolamine with menaquinone- triggered apoptosis in an in vitro model of leukemia'.
Answer: Altered metabolism is increasingly acknowledged as an important aspect of cancer, and thus serves as a potentially fertile area for the identification of therapeutic targets or leads. Our recent work using transcriptional data to predict metabolite levels in cancer cells led to preliminary evidence of the antiproliferative role of menaquinone (vitamin K2) in the Jurkat cell line model of acute lymphoblastic leukemia. However, nothing is known about the direct metabolic impacts of menaquinone in cancer, which could provide insights into its mechanism of action. Here, we used metabolomics to investigate the process by which menaquinone exerts antiproliferative activity on Jurkat cells. We first validated the dose-dependent, semi-selective, pro-apoptotic activity of menaquinone treatment on Jurkat cells relative to non-cancerous lymphoblasts. We then used mass spectrometry-based metabolomics to identify systems-scale changes in metabolic dynamics that are distinct from changes induced in noncancerous cells or by other chemotherapeutics. One of the most significantly affected metabolites was phosphoethanolamine, which exhibited a two-fold increase in menaquinone-treated Jurkat cells compared to vehicle-treated cells at 24 h, growing to a five-fold increase at 72 h. Phosphoethanolamine elevation was observed prior to the induction of apoptosis, and was not observed in menaquinonetreated lymphoblasts or chemotherapeutic-treated Jurkat cells. We also validated the link between menaquinone and phosphoethanolamine in an ovarian cancer cell line, suggesting potentially broad applicability of their relationship. This metabolomics-based work is the first detailed characterization of the metabolic impacts of menaquinone treatment and the first identified link between phosphoethanolamine and menaquinone-induced apoptosis.
Question: Write a study description for the study titled 'Maternal chromium propionate reprograms the gut-blood-placenta axis to support neonatal immune and metabolic development in dairy calves: a multi-omics insight'.
Answer: This study sequenced the non-target metabolome of maternal plasma samples from dairy cows to investigate the effect of chromium propionate supplementation on maternal plasma metabolism in the pre-peripartum period.