LuYuxing/MetaBench huggingface dataset:
Question: Write a study description for the study titled 'A polyamine-centric blood-based metabolite panel predictive of poor response to CAR T-cell therapy in large B cell lymphoma'.
Answer: Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory (r/r) large B-cell lymphoma (LBCL) results in durable response in only a subset of patients. MYC overexpression in LBCL tumors is associated with poor response to treatment. We tested whether a MYC-driven polyamine signature, as a liquid biopsy, is predictive of response to anti-CD19 CAR-T therapy in patients with r/r LBCL. Elevated plasma acetylated polyamines were associated with non-durable response. Concordantly, increased expression of spermidine synthase, a key enzyme which regulates levels of acetylated spermidine, was prognostic for survival in r/r LBCL. A broad metabolite screen identified additional markers which resulted in a 6-marker panel (6MetP) consisting of acetylspermidine, diacetylspermidine and lysophospholipids which was validated in an independent set from another institution as predictive of non-durable response to CAR T therapy. A polyamine centric metabolomics liquid biopsy panel has predictive value for response to CAR-T therapy in r/r LBCL.
Question: Write a study description for the study titled 'Exploring the Role of Gut Microbiota and Metabolomic Changes on Singing in Zebra Finches'.
Answer: Recent studies have demonstrated that the cognitive abilities of songbirds are linked to gut microbiome beta diversity. To explore whether the gut microbiome influences vocalization, a cognitive trait, we examined how antibiotics impact metabolism, microbiome and singing behavior in adult male zebra finches. Using untargeted liquid chromatography-mass spectrometry and metagenomic sequencing, we observed significant changes in stool metabolites, microbiome composition and vocal behavior after 14 days of antibiotic treatment. Metabolomic analysis revealed disruptions in the alanine, aspartate and glutamate pathways post-treatment. Furthermore, an analysis of phyla in the gut microbiome demonstrated a decrease in Firmicutes and an increase in Bacteroidetes. Treated birds sang fewer female-directed (FD) songs and produced more introductory notes compared to controls, suggesting possible alterations in neural pathways tied to motivation and vocalization. Despite the decrease in their number, the spectral and temporal properties of FD songs remained stable. Our findings suggest that antibiotic-induced changes in the gut microbiome may influence complex social behaviors such as vocal communication in zebra finches.
Question: Write a study description for the study titled 'Interaction of Genetic Variants Activates Latent Metabolic Pathways in Yeast'.
Answer: Genetic interactions are fundamental to the architecture of complex traits, yet the molecular mechanisms by which variant combinations influence cellular pathways remain poorly understood. Here, we answer the question of whether interactions between genetic variants can activate unique pathways and if such pathways can be targeted to modulate phenotypic outcomes. The model organism Saccharomyces cerevisiae was used to dissect how two causal SNPs, MKT1(89G) and TAO3(4477C), interact to modulate metabolic and phenotypic outcomes during sporulation. By integrating time-resolved transcriptomics, absolute proteomics, and targeted metabolomics in isogenic allele replacement yeast strains, we show that the combined presence of these SNPs uniquely activates the arginine biosynthesis pathway and suppresses ribosome biogenesis, reflecting a metabolic trade-off that enhances sporulation efficiency. Functional validation demonstrates that the arginine pathway is essential for mitochondrial activity and efficient sporulation only in the double-SNP background. Our findings show how genetic variant interactions can rewire core metabolic networks, providing a mechanistic framework for understanding polygenic trait regulation and the emergence of additive effects in complex traits.
Question: Write a study description for the study titled 'A robust method for performing 1H-NMR lipidomics in embryonic zebrafish'.
Answer: The embryonic zebrafish is an ideal system for lipid analyses with relevance to many areas of bioscience research, including biomarkers and therapeutics. Research in this area has been hampered by difficulties in extracting, identifying and quantifying lipids. We employed 1H-NMR at 700MHz to profile lipids in developing zebrafish embryos. The optimal method for lipidomics in embryonic zebrafish incorporated rapid lipid extraction using chloroform and an environment without oxygen depletion. Pools of 10 embryos gave the most acceptable signal-to-noise ratio, and the inclusion of chorions in the sample had no significant effect on lipid abundances. Embryos, bisected into cranial (head and yolk sac) and caudal (tail) regions, were compared by principal component analysis and analysis of variance.
Question: Write a study description for the study titled 'Effects of Yulin Tong Bu formula on modulating gut microbiota and fecal metabolite interactions in mice with polycystic ovary syndrome'.
Answer: BACKGROUND: Polycystic ovarian syndrome (PCOS) is a common endocrine disorder characterized by hyperandrogenism, ovarian dysfunction and polycystic ovarian morphology. Gut microbiota dysbiosis and metabolite are associated with PCOS clinical parameters. Yulin Tong Bu formula (YLTB), a traditional Chinese medicine formula, has been recently indicated to be capable of ameliorating polycystic ovary symptoms and correcting abnormal glucose metabolism. However, the therapeutic mechanism of YLTB on PCOS has not been fully elucidated.METHODS: A pseudo sterile mouse model was established during this 4-day acclimatization phase by giving the animals an antibiotic cocktail to remove the gut microbiota. Here, the therapeutic effects of YLTB on PCOS were investigated using dehydroepiandrosterone plus high-fat diet induced PCOS mice model. Female prepuberal mice were randomly divided into 3 groups; namely, the control group, PCOS group and YLTB (38.68 g/kg/day) group. To test whether this effect is associated with the gut microbiota, we performed 16S rRNA sequencing studies to analyze the fecal microbiota of mice. The relationships among metabolites, gut microbiota and PCOS phenotypes were further explored by using Spearman correlation analysis. Then, the effect of metabolite ferulic acid was then validated in PCOS mice.RESULTS: Our results showed that YLTB treatment ameliorated PCOS features (ovarian dysfunction, delayed glucose clearance, decreased insulin sensitivity, deregulation of glucolipid metabolism and hormones, etc) and significantly attenuated PCOS gut microbiota dysbiosis. Spearman correlation analysis showed that metabolites such as ferulic acid and folic acid are negatively correlated with PCOS clinical parameters. The effect of ferulic acid was similar to that of YLTB. In addition, the bacterial species such as Bacteroides dorei and Bacteroides fragilis were found to be positively related to PCOS clinical parameters, using the association study analysis.CONCLUSION: These results suggest that YLTB treatment systematically regulates the interaction between the gut microbiota and the associated metabolites to ameliorate PCOS, providing a solid theoretical basis for further validation of YLTB effect on human PCOS trials.
Question: Write a study description for the study titled 'Novel automated workflow for spectral alignment and mass calibration in MS imaging using a sputtered Ag nanolayer'.
Answer: Mass spectrometry imaging (MSI) is a technique that can map analyte spatial distribution directly onto a tissue section. This enables the spatial correlation of molecular entities with a tissue morphology to be investigated. Analyte annotation in MSI is intrinsically linked to the mass accuracy of the data. Mass accuracy and analyte identification are determined by such factors as the experimental set up and the data processing workflow. We present an MSI data processing workflow that uses a label-free approach to compensate for mass shifts. The algorithms developed were designed to perform efficiently even for datasets much larger than computer's memory. Herein, we present the application of the developed processing workflow to a dataset with more than 13.000 pixels and ∼50.000 mass channels. We assessed the overall mass accuracy in the range m/z 400 to 1200 using silver and gold sputtered nanolayers. With our novel processing workflow we were able to obtain mass errors as low as 5 ppm using a TOF instrument.
Question: Write a study description for the study titled 'Cell of origin epigenetic priming determines susceptibility to Tet2 mutation'.
Answer: Hematopoietic stem cell (HSC) mutations can result in clonal hematopoiesis (CH) with heterogeneous clinical outcomes. Here, we investigated how the cell state preceding Tet2 mutation impacts the pre-malignant phenotype. Using an inducible system for clonal analysis of myeloid progenitors, we found that the epigenetic features of clones at similar differentiation status were highly heterogeneous and functionally responded differently to Tet2 mutation. Cell differentiation stage also influenced Tet2 mutation response indicating that the cell of origin's epigenome modulates clone-specific behaviors in CH. Molecular features associated with higher risk outcomes include Sox4 that sensitized cells to Tet2 inactivation, inducing dedifferentiation, altered metabolism and increasing the in vivo clonal output of mutant cells, as confirmed in primary GMP and HSC models. Our findings validate the hypothesis that epigenetic features can predispose specific clones for dominance, explaining why identical genetic mutations can result in different phenotypes.
Question: Write a study description for the study titled 'UPLC-QTOF-MS-Based Plasma Lipidomic Profiling Reveals Biomarkers for Inflammatory Bowel Disease Diagnosis'.
Answer: Identification of new biomarkers may help in the early diagnosis of inflammatory bowel disease (IBD). In this study, ultrahigh-performance liquid chromatography equipped with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was used to analyze the untargeted lipidomics and compare plasma lipid profiles between IBD patients and control subjects. The principal component analysis and partial least-squares-discriminant analysis were carried out to distinguish IBD patients from control subjects. Using univariate and multivariate analysis, 55 significantly different metabolites from five lipid classes, fatty acyls (n = 19), glycerophospholipids (n = 5), prenol lipids (n = 10), sphingolipids (n = 2), and sterol lipids (n = 19) were identified. Forty-four of the 55 metabolites were analyzed by receiver operating characteristic (ROC) curve and area under curve (AUC) of >0.80. After validation in an independent cohort, IBD patients were differentiated from the control subjects by significantly altered plasma level of palmitic acid, 7alpha, 25-dihydroxycholesterol, 20-hydroxyeicosatetraenoic (HETE)-d6, (+/-)5,6-epoxy-eicosatrienoic acid (EpETrE), docosahexaenoic acid (DHA), 9-heptadecylenic acid, lactucaxanthin, α-carotene, traumatic acid, and neoquassin with both sensitivity and specificity above 80%. Pathway analysis suggested that IBD dysregulation was related to the biosynthesis of primary bile acid, the metabolism of arachidonic acid, the metabolism of sphingolipid, fatty acid elongation, and glycerophospholipid metabolism. Our results suggest that the lipidomic profiling of patients plasma could be a potential method for IBD diagnosis.
Question: Write a study description for the study titled 'Parallel single-cell metabolic analysis and extracellular vesicle profiling reveal vulnerabilities with prognostic significance in acute myeloid leukemia (Metabolomic analysis on extracellular vesicles)'.
Answer: Acute myeloid leukemia (AML) is an aggressive disease with a high relapse rate. In this study, we map the metabolic profile of CD34+(CD38low/-) AML cells and the extracellular vesicle signatures in circulation from AML patients at diagnosis. CD34+ AML cells display high antioxidant glutathione levels and enhanced mitochondrial functionality, both associated with poor clinical outcomes. Although CD34+ AML cells are highly dependent on glucose oxidation and glycolysis for energy, those from intermediate- and adverse-risk patients reveal increased mitochondrial dependence. Extracellular vesicles from AML are mainly enriched in stem cell markers and express antioxidant GPX3, with their profiles showing potential prognostic value. Extracellular vesicles enhance mitochondrial functionality and dependence on CD34+ AML cells via the glutathione/GPX4 axis. Notably, only extracellular vesicles from adverse-risk patients enhance leukemia cell engraftment in vivo. Here, we show a potential noninvasive approach based on liquid ‘cell-extracellular vesicle’ biopsy toward a redefined metabolic stratification in AML.Metabolomic analysis on extracellular vesicles is reported in the current study MTBLS11746.Lipidomic analysis on extracellular vesicles is reported in MTBLS11523.
Question: Write a study description for the study titled 'Liquid chromatography coupled to high-resolution mass spectrometry metabolomics: A useful tool for investigating tumor secretome based on a three-dimensional co-culture model'.
Answer: Three-dimensional (3D) cell culture technologies, which more closely mimic the complex microenvironment of tissue, are being increasingly evaluated as a tool for the preclinical screening of clinically promising new molecules, and studying of tissue metabolism. Studies of metabolites released into the extracellular space (secretome) allow understanding the metabolic dynamics of tissues and changes caused by therapeutic interventions. Although quite advanced in the field of proteomics, studies on the secretome of low molecular weight metabolites (< 1500 Da) are still very scarce. We present an untargeted metabolomic protocol based on the hybrid technique of liquid chromatography coupled with high-resolution mass spectrometry for the analysis of low-molecular-weight metabolites released into the culture medium by 3D cultures and co-culture (secretome model). For that we analyzed HT-29 human colon carcinoma cells and 3T3-L1 preadipocytes in 3D-monoculture and 3D-co-culture. The putative identification of the metabolites indicated a sort of metabolites, among them arachidonic acid, glyceric acid, docosapentaenoic acid and beta-Alanine which are related to cancer and obesity. This protocol represents a possibility to list metabolites released in the extracellular environment in a comprehensive and untargeted manner, opening the way for the generation of metabolic hypotheses that will certainly contribute to the understanding of tissue metabolism, tissue-tissue interactions and metabolic responses to the most varied interventions. Moreover, it brings the potential to determine novel pathways and accurately identify biomarkers in cancer and other diseases. The metabolites indicated in our study have a close relationship with the tumor microenvironment in accordance with the literature review.
Question: Write a study description for the study titled 'A Metabolic Profiling Strategy for the Dissection of Plant Defense against Fungal Pathogens (DI-MS assays)'.
Answer: Here we present a metabolic profiling strategy employing direct infusion Orbitrap mass spectrometry (MS) and gas chromatography-mass spectrometry (GC/MS) for the monitoring of soybean's (Glycine max L.) global metabolism regulation in response to Rhizoctonia solani infection in a time-course. Key elements in the approach are the construction of a comprehensive metabolite library for soybean, which accelerates the steps of metabolite identification and biological interpretation of results, and bioinformatics tools for the visualization and analysis of its metabolome. The study of metabolic networks revealed that infection results in the mobilization of carbohydrates, disturbance of the amino acid pool, and activation of isoflavonoid, α-linolenate and phenylpropanoid biosynthetic pathways. Components of these pathways include phytoalexins, coumarins, flavonoids, signaling molecules, and hormones, many of which exhibit antioxidant properties and bioactivity helping the plant to counterattack the pathogen's invasion. Unraveling the biochemical mechanism operating during soybean-Rhizoctonia interaction in addition to its significance towards the understanding of the plant's metabolism regulation under biotic stress, provides valuable insights with potential for applications in biotechnology, crop breeding, and agrochemical and food industries.
Question: Write a study description for the study titled 'Hyperhomocysteinemia-related serum metabolome alterations not normalized by short-term folic acid treatment'.
Answer: IntroductionHyperhomocysteinemia (HHCys) is an independent risk factor for various diseases such as cardiovascular diseases, Alzheimer's, and cancers. Folate deficiency is one of the significant reasons for HHCys. However, it is not known whether folate deficiency with HHCys is associated with any serum metabolites.ObjectivesOur objective was to identify the metabolic alterations in people having folate deficiency with HHCys and check whether a short-term folic acid therapy could reverse those metabolic changes.MethodsThe study enrolled 34 participants aged between 18 and 40 years having folate deficiency ( 15 μmol/L) and 21 normal healthy individuals. A short-term intervention of oral folic acid (5 mg/day) was done in the HHCys group for 30 days. Untargeted metabolomics analysis of serum was performed in all study subjects before and after the folic acid treatment. Different univariate methods and the multivariable-adjusted linear regression models were employed to determine an association between homocysteine level and metabolite profile.ResultsMetabolomics analysis data showed that many metabolites involved in the biochemical pathways of lipid metabolisms such as polyunsaturated fatty acids, glycerolipids, and phospholipids were downregulated in the HHCys group. Short-term oral folic acid therapy significantly reduced their serum homocysteine level. However, the metabolic pathway alterations observed in folate-deficient HHCys-condition were unaltered even after the folic acid treatment.ConclusionsOur study revealed that people who have a folic acid deficiency with HHCys have an altered metabolite profile related to lipid metabolism, which cannot be reversed by short-term folic acid therapy.
Question: Write a study description for the study titled 'Fecal metabolites in sows of different reproductive potential'.
Answer: Placental dysplasia critically impairs fetal growth and development by disrupting nutrient supply. Thiamine, predominantly in its bioactive form thiamine pyrophosphate, serves as an essential coenzyme in mitochondrial energy metabolism, yet its regulatory role in placental development remains elusive.ObjectivesThis study systematically unraveled the metabolic network disparities between sows with different reproductive potentials and elucidates the mechanisms by which characterized metabolites enhance placental angiogenesis and nutrient transport efficiency to promote fetal development.MethodsWe initially analyzed plasma and fecal metabolite composition and fecal microbial composition of sows with high and low reproductive potential by 16S rRNA sequencing and untargeted metabolomics. Subsequently, we evaluated the effects of thiamine, the identified characterized metabolite, on the angiogenesis and nutrient transport functions of placenta and the growth and development of offspring in a rat model, as well as verified the effects of thiamine on the cell migration of placental trophoblast cells by in vitro experiment.ResultsSows with high reproductive potential exhibit a distinct metabolic profile with significantly elevated plasma arginine and fecal thiamine levels and the abundance of gut thiamine-synthesizing bacteria increases in parallel. Maternal thiamine supplementation effectively promotes offspring growth and enhances thiamine metabolism in the maternal-placental-fetal axis. Meanwhile, thiamine improves placental function by increasing thiamine-related metabolic enzymes and acetyl-CoA content in the placenta. Furthermore, thiamine facilitates placental angiogenesis via activation of the Notch signaling pathway and initiates the Notch-PI3K/AKT cascade reaction, which regulates placental nutrient metabolism efficiency and transporter expression.ConclusionsMaternal supplementation with thiamine during gestation and lactation promotes placental development and enhances offspring growth through activation of the Notch signaling pathway.
Question: Write a study description for the study titled 'IDH1 Mutations Induce Organelle Defects Via Dysregulated Phospholipids (CSHpos)'.
Answer: Infiltrating gliomas are devastating and incurable tumors. Amongst all gliomas, those harboring an isocitrate dehydrogenase 1 mutation (IDHmut), acquire a different tumor biology and clinical manifestation than those that are IDHWT. Understanding the unique metabolic profile reprogrammed by IDH1 mutation has the potential to identify new molecular targets for glioma therapy. Herein, we discovered monounsaturated (MUFA) to polyunsaturated (PUFA) lipid imbalances in organelles, generated by IDH mutation in cells and patient tissue, that were responsible for Golgi and ER dilation. We demonstrated a direct link between the IDH mutation and these organelle morphology via D-2HG-induced stearyl-CoA desaturase (SCD) overexpression, the rate limiting enzyme in MUFA biosynthesis. Inhibition of IDH mutation or SCD silencing restored ER and Golgi morphology, while D-2HG and oleic acid induced morphological defects in these organelles. Moreover, addition of oleic acid, which tilted the balance towards elevated levels of MUFA, produced IDH1mut-specific cellular apoptosis. Collectively, these results suggest that IDH1mut-induced SCD overexpression can rearrange the biodistribution of lipids in the organelles of glioma, providing a new insight on the link between lipids metabolism and organelle morphology in these cells, with potential and unique therapeutic implications.Linked studies;MTBLS1967 FA_HILICZMTBLS1973 LCMS(CSHNeg)