LuYuxing/MetaBench huggingface dataset:
Question: Write a study description for the study titled 'A comprehensive multiomic analysis reveals metabolic reprogramming underlying human Fontan-associated liver disease'.
Answer: BACKGROUND: Single ventricle congenital heart disease (SVCHD) is a severe form of cardiac malformation in which there is only one functional ventricle. The Fontan operation is the current standard of care for SVCHD. Almost all patients who have undergone the Fontan operation develop liver fibrosis at a young age, resulting in a condition known as Fontan-associated liver disease (FALD). The pathogenesis and mechanisms underlying FALD remain little understood, hindering development of effective therapies.OBJECTIVES: We aimed to present a comprehensive multiomic analysis of human FALD, thereby revealing the fundamental biology and pathogenesis of FALD. METHODS: We recently generated a single-cell transcriptomic and epigenomic atlas of human FALD using snRNA-ATAC-seq, which revealed profound metabolic reprogramming in FALD. Here we applied liquid chromatography-mass spectrometry (LC-MS) based untargeted metabolomics to unveil the metabolomic landscape of human FALD, using liver samples/biopsies from age and gender-matched healthy donors and FALD patients (n=12 per group). Extracted liver metabolites were analyzed by C18 high performance liquid chromatography (HPLC) and hydrophilic interaction chromatography (HILIC) followed by high resolution MS on Orbitrap. Statistical and bioinformatics analyses were performed to identify altered metabolites and metabolic pathways in FALD. These results were integrated with recently published snRNA-ATAC-seq and serum metabolomics datasets to present a comprehensive multiomic atlas of FALD. RESULTS: We discovered profound metabolic abnormalities in livers of patients with early-stage FALD, particularly amino acid metabolism, peroxisomal fatty acid oxidation, cytochrome P450 system, glycolysis, TCA cycle, ketone body metabolism and bile acids metabolism. Integrated analyses with liver snRNA-ATAC-seq and serum metabolomics data unveiled the transcriptional mechanisms driving this metabolic reprogramming and the crosstalk between liver and the rest of the body. Comparison with human metabolic dysfunction-associated fatty liver disease (MAFLD) and metabolic dysfunction-associated steatohepatitis (MASH) revealed dysregulated amino acid metabolism as a common metabolic abnormality. CONCLUSIONS: Our comprehensive multiomic atlas of human FALD reveals the fundamental biology and pathogenesis mechanisms of FALD.
Question: Write a study description for the study titled 'Metabolite profiling in LC-DAD using multivariate curve resolution: the alsace package in R'.
Answer: For those chemical compounds absorbing in the UV–Vis region and not readily applicable to routine mass spectrometry ionisation methods, liquid chromatography coupled to diode array detection is a convenient platform to perform metabolite profiling. Data processing by hand is labour-intensive and error prone. In the present study a strategy based on multivariate curve resolution, and its implementation in an R package called alsace are described. The final result of an analysis is a table containing peak heights or peak areas for all features of the individual injections. The capabilities of the software, providing elements such as splitting the data into separate, possibly overlapping time windows, merging the results of the individual time windows, and parametric time warping to align features, are illustrated using a cassava-derived data set.
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 (UPLC-MS 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.  UPLC-MS protocols and data are reported in the current study MTBLS465.  NMR protocols and data associated to this study are reported in MTBLS470.  Linked Studies: MTBLS470
Question: Write a study description for the study titled 'Critical shifts in lipid metabolism promote megakaryocyte differentiation and proplatelet formation (Shotgun lipidomics assays without inhibition)'.
Answer: During megakaryopoiesis, megakaryocytes (MK) undergo cellular morphological changes with strong modification of membrane composition and lipid signaling. Here we adopt a lipid-centric multi-omics approach to create a quantitative map of the MK lipidome during maturation and proplatelet formation. Data reveal that MK differentiation is driven by an increased fatty acyl import and de novo lipid synthesis, resulting in an anionic membrane phenotype. Pharmacological perturbation of fatty acid import and phospholipid synthesis blocked membrane remodeling and directly reduced MK polyploidization and proplatelet formation resulting in thrombocytopenia. The anionic lipid shift during megakaryopoiesis was paralleled by lipid-dependent relocalization of the scaffold protein CKIP-1 and recruitment of the kinase CK2α to the plasma membrane, which seems to be essential for sufficient platelet biogenesis. Overall, this study provides a framework to understand how the MK lipidome is altered during maturation and the impact of MK membrane lipid remodeling on MK kinase signaling involved in thrombopoiesis.Shotgun lipidomics assays without inhibition are reported in the current study MTBLS6082Shotgun lipidomics assays after inhibition with FSG67 and Triacsin C are reported in MTBLS6083Targeted lipidomics assay without inhibition are reported in MTBLS6084
Question: Write a study description for the study titled 'Rapid identification of species, sex and maturity by mass spectrometric analysis of animal faeces'.
Answer: BACKGROUND: We describe a new approach to the recovery of information from faecal samples, based on the analysis of the molecular signature generated by rapid evaporative ionisation mass spectrometry (REIMS).RESULTS: Faecal pellets from five different rodent species were analysed by REIMS, and complex mass spectra were acquired rapidly (typically a few seconds per sample). The uninterpreted mass spectra (signatures) were then used to seed linear discriminant analysis and classification models based on random forests. It was possible to classify each species of origin with a high rate of accuracy, whether faeces were from animals maintained under standard laboratory conditions or wild-caught. REIMS signatures were stable to prior storage of the faecal material under a range of different conditions and were not altered rapidly or radically by changes in diet. Further, within species, REIMS signatures could be used to discriminate faeces from adult versus juvenile mice, male versus female mice and those from three different laboratory strains.CONCLUSIONS: REIMS offers a completely novel method for the rapid analysis of faecal samples, extending faecal analysis (previously focused on DNA) to an assessment of phenotype, and has considerable potential as a new tool in the armamentarium of the field biologist.
Question: Write a study description for the study titled 'Plasma Lipidomics Identifies Anticedent Memory Impairment in Older Adults'.
Answer: Alzheimer's disease causes a progressive dementia that currently affects over 35 million individuals worldwide and is expected to affect 115 million by 2050 (ref. 1). There are no cures or disease-modifying therapies, and this may be due to our inability to detect the disease before it has progressed to produce evident memory loss and functional decline. Biomarkers of preclinical disease will be critical to the development of disease-modifying or even preventative therapies. Unfortunately, current biomarkers for early disease, including cerebrospinal fluid tau and amyloid-β levels, structural and functional magnetic resonance imaging and the recent use of brain amyloid imaging or inflammaging, are limited because they are either invasive, time-consuming or expensive. Blood-based biomarkers may be a more attractive option, but none can currently detect preclinical Alzheimer's disease with the required sensitivity and specificity. Herein, we describe our lipidomic approach to detecting preclinical Alzheimer's disease in a group of cognitively normal older adults. We discovered and validated a set of ten lipids from peripheral blood that predicted phenoconversion to either amnestic mild cognitive impairment or Alzheimer's disease within a 2-3 year timeframe with over 90% accuracy. This biomarker panel, reflecting cell membrane integrity, may be sensitive to early neurodegeneration of preclinical Alzheimer's disease.
Question: Write a study description for the study titled 'Simultaneous Membrane and RNA Binding by Tick-Borne Encephalitis Virus Capsid Protein'.
Answer: Tick-borne encephalitis virus is an enveloped, pathogenic, RNA virus in the family Flaviviridae, genus Flavivirus. Viral particles are formed when the nucleocapsid, consisting of an RNA genome and multiple copies of the capsid protein, buds through the endoplasmic reticulum membrane and acquires the viral envelope and the associated proteins. The coordination of the nucleocapsid components to the sites of assembly and budding are poorly understood. Here, we investigate nucleocapsid assembly by characterizing the interactions of the wild-type and truncated capsid proteins with membranes by using biophysical methods and model membrane systems. We show that capsid protein initially binds membranes via electrostatic interactions with negatively-charged lipids which is followed by membrane insertion. Additionally, we show that membrane-bound capsid protein can recruit viral genomic RNA. We confirm the biological relevance of the biophysical findings by using mass spectrometry to show that purified virions contain negatively-charged lipids. Our results suggest that nucleocapsid assembly is coordinated by negatively-charged membrane patches on the endoplasmic reticulum and that the capsid protein mediates direct contacts between the nucleocapsid and the membrane.
Question: Write a study description for the study titled 'OPA1 promotes ferroptosis by augmenting mitochondrial ROS and suppressing an integrated stress response'.
Answer: Ferroptosis, an iron-dependent form of nonapoptotic cell death mediated by lipid peroxidation, has been implicated in the pathogenesis of multiple diseases. Subcellular organelles play pivotal roles in the regulation of ferroptosis, but the mechanisms underlying the contributions of the mitochondria remain poorly defined. Optic atrophy 1 (OPA1) is a mitochondrial dynamin-like GTPase that controls mitochondrial morphogenesis, fusion and energetics. Here, we report that human and mouse cells lacking OPA1 are markedly resistant to ferroptosis. Reconstitution with OPA1 mutants demonstrates that ferroptosis sensitization requires the GTPase activity but is independent of OPA1-mediated mitochondrial fusion. Mechanistically, OPA1 confers susceptibility to ferroptosis by maintaining mitochondrial homeostasis and function, which contributes both to the generation of mitochondrial lipid reactive oxygen species (ROS) and suppression of an ATF4-mediated integrated stress response. Together, these results identify an OPA1-controlled mitochondrial axis of ferroptosis regulation and provide mechanistic insights for therapeutically manipulating this form of cell death in diseases.
Question: Write a study description for the study titled 'Metabolomic Profiling Reveals Key Metabolic Alterations in MCF7 Tamoxifen-Resistant Cells Following EPAS1 Inhibition'.
Answer: This study aims to investigate the metabolic alterations associated with acquired tamoxifen (TAM) resistance in luminal A breast cancer cells. Using untargeted LC-MS/MS metabolomics, we compared parental MCF7 and TAM-resistant MCF7/Tam1 cells to identify key metabolic pathways affected by EPAS1 (HIF-2α)-mediated hypoxia-driven reprogramming. The study further evaluates the impact of EPAS1 inhibition by PT2977 on the reversal of these metabolic changes and restoration of TAM sensitivity.
Question: Write a study description for the study titled 'Metabolite signatures of diverse Camellia sinensis tea populations'.
Answer: Tea plants (Camellia sinensis) present an excellent system to study evolution and diversification of specialized metabolites due to their abundance in classes, numbers and contents. A large number of tea cultivars have been cultivated throughout the world not only because of their adaption to different environments but of selection for specific flavors. The chemical and genetic basis for unique taste and aroma of different tea cultivars remains largely unknown, but is critical for guiding genetic breeding of new cultivars. Using transcriptomic data from 136 representative tea accessions in China, we obtain 925,854 high-quality single-nucleotide polymorphisms (SNPs) useful for marker-assisted breeding. Phylogenetic and population structure analyses separate sampled tea accessions into five major groups. Different major alleles are identified on 1183 SNP sites for the two major types of tea, C. sinensis var. assamica (CSA) and C. sinensis var. sinensis (CSS), reflecting fixation of these alleles after population divergence. Non-targeted metabolomic analyses detect 2,818 and 2,311 metabolic features in tea samples in positive and negative ionization modes, respectively, including 355 and 286 metabolites respectively that are differentially accumulated in different tea groups. Each phylogenetic group contains signature metabolites. In particular, CSA tea accessions are featured with high accumulation of diverse classes of flavonoid compounds, such as flavanols, flavonol mono-/di-glycosides and proanthocyanidin dimers. Comparisons of gene expression profiles of different tea groups identify hundreds of differentially expressed genes with some involved in the biosynthesis of characteristic tea metabolites, reflecting a combinational effect of genetic and environmental factors. Taken together, our study provides new insights into the phylogenetic relationships, molecular markers, metabolite compositions, and gene expression profiles of representative cultivated tea accessions in China, which are beneficial for targeted tea breeding and improvement.
Question: Write a study description for the study titled 'Stage-specific roles of microbial dysbiosis and metabolic disorders in rheumatoid arthritis'.
Answer: OBJECTIVE: Rheumatoid arthritis (RA) is a progressive disease including four stages, where gut microbiome is associated with pathogenesis. We aimed to investigate stage-specific roles of microbial dysbiosis and metabolic disorders in RA.METHODS: We investigated stage-based profiles of faecal metagenome and plasma metabolome of 76 individuals with RA grouped into four stages (stages I-IV) according to 2010 RA classification criteria, 19 individuals with osteroarthritis and 27 healthy individuals. To verify bacterial invasion of joint synovial fluid, 16S rRNA gene sequencing, bacterial isolation and scanning electron microscopy were conducted on another validation cohort of 271 patients from four RA stages.RESULTS: First, depletion of Bacteroides uniformis and Bacteroides plebeius weakened glycosaminoglycan metabolism (p<0.001), continuously hurting articular cartilage across four stages. Second, elevation of Escherichia coli enhanced arginine succinyltransferase pathway in the stage II and stage III (p<0.001), which was correlated with the increase of the rheumatoid factor (p=1.35 x 10^-3) and could induce bone loss. Third, abnormally high levels of methoxyacetic acid (p=1.28 x 10^-8) and cysteine-S-sulfate (p=4.66 x 10^-12) inhibited osteoblasts in the stage II and enhanced osteoclasts in the stage III, respectively, promoting bone erosion. Fourth, continuous increase of gut permeability may induce gut microbial invasion of the joint synovial fluid in the stage IV.CONCLUSIONS: Clinical microbial intervention should consider the RA stage, where microbial dysbiosis and metabolic disorders present distinct patterns and played stage-specific roles. Our work provides a new insight in understanding gut-joint axis from a perspective of stages, which opens up new avenues for RA prognosis and therapy.
Question: Write a study description for the study titled 'Single-cell RNA sequencing decipher hepatic injury and APOA4 as a biomarker in males with intrauterine growth restriction'.
Answer: Intrauterine growth restriction (IUGR) is associated with increased relative liver weight at birth, hepatic function decline and a higher risk for chronic liver and cardiovascular diseases in adults. Precise mechanisms of early developmental plasticity to intervene in poor fetal programming and adult disease remain largely elusive and warrant extensive research. Selecting natural piglets’ model of IUGR, using the liver as a readout and combining previous transcriptome findings, a map of cellular landscape was created to reveal a sex-dependent manner in IUGR-induced hepatic injury and its long-term functional repercussions. At the one-week postnatal node, we reveal that in contrast to a converting trend about an immune-adapted phenotype in female IUGRs, the more severe hepatic injury in male IUGRs is attributed to persistent inflammation caused by abnormal lipid metabolism, which disrupts the interactions of non-immune cells, resulting in impaired liver regeneration lasting into adulthood. In addition, we consider APOA4 as a new biomarker for the detection of IUGRs and discover its underlying role in hypoxic conditions. Our study opens the possibility to early therapy and screening of gender-specific hepatic injury brought on by IUGR.
Question: Write a study description for the study titled 'Cell type-specific proteomics uncovers a RAF15-SnRK2.6/OST1 kinase cascade in guard cells'.
Answer: Multicellular organisms such as plants contain various cell types with specialized functions. Analyzing the characteristics of each cell type reveals specific cell functions and enhances our understanding of organization and function at the organismal level. Guard cells (GCs) are specialized epidermal cells that regulate the movement of the stomata and gaseous exchange, and provide a model genetic system for analyzing cell fate, signaling and function. Several proteomics analyses of GC are available, but these are limited in depth. Here we used enzymatic isolation and flow cytometry to enrich GC and mesophyll cell protoplasts and perform in-depth proteomics in these two major cell types in Arabidopsis leaves. We identified approximately 3000 proteins not previously found in the GC proteome and more than 600 proteins that may be specific to GC. The depth of our proteomics enabled us to uncover a guard cell-specific kinase cascade whereby Raf15 and Snf1-related kinase2.6 (SnRK2.6)/OST1(open stomata 1) mediate abscisic acid (ABA)-induced stomatal closure. RAF15 directly phosphorylated SnRK2.6/OST1 at the conserved Ser175 residue in its activation loop and was sufficient to reactivate the inactive form of SnRK2.6/OST1. ABA-triggered SnRK2.6/OST1 activation and stomatal closure was impaired in raf15 mutants. We also showed enrichment of enzymes and flavone metabolism in GC, and consistent, dramatic accumulation of flavone metabolites. Our study answers the long-standing question of how ABA activates SnRK2.6/OST1 in GCs and represents a resource potentially providing further insights into the molecular basis of GC and mesophyll cell development, metabolism, structure and function.
Question: Write a study description for the study titled 'Circulating Metabolites in Progression to Islet Autoimmunity and Type 1 Diabetes'.
Answer: AIMS/HYPOTHESIS: Metabolic dysregulation may precede the onset of type 1 diabetes. However, these metabolic disturbances and their specific role in disease initiation remain poorly understood. In this study, we examined whether children who progress to type 1 diabetes have a circulatory polar metabolite profile distinct from that of children who later progress to islet autoimmunity but not type 1 diabetes and a matched control group.METHODS: We analysed polar metabolites from 415 longitudinal plasma samples in a prospective cohort of children in three study groups: those who progressed to type 1 diabetes; those who seroconverted to one islet autoantibody but not to type 1 diabetes; and an antibody-negative control group. Metabolites were measured using two-dimensional GC high-speed time of flight MS.RESULTS: In early infancy, progression to type 1 diabetes was associated with downregulated amino acids, sugar derivatives and fatty acids, including catabolites of microbial origin, compared with the control group. Methionine remained persistently upregulated in those progressing to type 1 diabetes compared with the control group and those who seroconverted to one islet autoantibody. The appearance of islet autoantibodies was associated with decreased glutamic and aspartic acids.CONCLUSIONS/INTERPRETATION: Our findings suggest that children who progress to type 1 diabetes have a unique metabolic profile, which is, however, altered with the appearance of islet autoantibodies. Our findings may assist with early prediction of the disease.