LuYuxing/MetaBench huggingface dataset:
Question: Write a study description for the study titled 'Fatty acid transport protein 4 is required for incorporation of saturated ultralong-chain fatty acids into epidermal ceramides and monoacylglycerols'.
Answer: Fatty acid transport protein 4 (FATP4) is an acyl-CoA synthetase that is required for normal permeability barrier in mammalian skin. FATP4 (SLC27A4) mutations cause ichthyosis prematurity syndrome, a nonlethal disorder. In contrast, Fatp4-/- mice die neonatally from a defective barrier. Here we used electron microscopy and lipidomics to characterize defects in Fatp4-/- mice. Mutants showed lamellar body, corneocyte lipid envelope, and cornified envelope abnormalities. Lipidomics identified two lipids previously speculated to be present in mouse epidermis, sphingosine β-hydroxyceramide and monoacylglycerol; mutants displayed decreased proportions of these and the two ceramide classes that carry ultralong-chain, amide-linked fatty acids (FAs) thought to be critical for barrier function, unbound ω-O-acylceramide and bound ω-hydroxyceramide, the latter constituting the major component of the corneocyte lipid envelope. Other abnormalities included elevated amounts of sphingosine α-hydroxyceramide, phytosphingosine non-hydroxyceramide, and 1-O-acylceramide. Acyl chain length alterations in ceramides also suggested roles for FATP4 in esterifying saturated non-hydroxy and β-hydroxy FAs with at least 25 carbons and saturated or unsaturated ω-hydroxy FAs with at least 30 carbons to CoA. Our lipidomic analysis is the most thorough such study of the Fatp4-/- mouse skin barrier to date, providing information about how FATP4 can contribute to barrier function by regulating fatty acyl moieties in various barrier lipids.
Question: Write a study description for the study titled 'RIOK1 Phase Separation Shapes Stress Adaptation and Cell Fate in Hepatocellular Carcinoma'.
Answer: Cancer cells can always be unexpected rescued from desperate environment by mounting adaptive responses to resolve the arising cellular stress. The dynamic stress granules (SGs) assembly and metabolic reprogramming play crucial roles in maintaining cellular growth and homeostasis. However, the mechanisms underlying their interaction remain elusive. Here we screened RIOK1 is highly expressed in liver cancer tissues and is transactivated by NRF2 under stressful conditions. Mechanistically, the oncogenic phenotype observed in hepatocellular carcinoma (HCC) cells is associated with the capacity of RIOK1 to undergo liquid-liquid phase separation. The non-enzymatic regulation of IGF2BP1 tyrosine phosphorylation by RIOK1 contributes to incorporating RIOK1/IGF2BP1/G3BP1 into stress granules which concurrently sequester PTEN mRNA. The decrease in PTEN translation concomitantly activates the pentose phosphate pathway to resolve stress and confer cytoprotection. Additionally, chidamide downregulates RIOK1 expression and enhances the efficacy of TKIs, presenting a promising therapeutic strategy for HCC treatment.
Question: Write a study description for the study titled 'Multi-omics systems toxicology study of mouse lung assessing the effects of aerosols from two heat-not-burn tobacco products and cigarette smoke'.
Answer: Cigarette smoke (CS) causes adverse health effects and leads to the development of respiratory disease (chronic obstructive pulmonary disease), cardiovascular disease, and cancer. To reduce the risk of smokers developing smoking-related diseases, Philip Morris International is developing modified risk tobacco products (MRTP). Within a systems toxicology study, we conducted an integrative multi-omics analysis to assess the effects of aerosols from two potential MRTPs - the Carbon Heated Tobacco Product (CHTP) 1.2 and the Tobacco Heating System (THS) 1.2 -, compared with cigarette smoke (CS) at matched nicotine concentrations, on the lung of ApoE-/- mice. Mice were exposed for up to six months and molecular exposure effects were measured by mRNA/miRNA transcriptomics, proteomics, metabolomics, and lipidomics. In addition, the impact of cessation (CESS) or switching to CHTP 1.2 (SWITCH) after three months of CS exposure was evaluated. This data set represents the lung metabolomics data obtained after 3 and 6 months of exposure. The 'Animal ID' or 'CAN' represents the unique animal identifier and allows matching of samples across the different data modalities.
Question: Write a study description for the study titled 'CYP46A1 promotes Parkinson’s disease'.
Answer: Parkinson’s disease (PD) is a neurodegenerative disease characterized by the death of dopaminergic neurons in the substantia nigra and the formation of Lewy bodies that are composed of aggregated α-synuclein (α-Syn). However, the factors that regulate α-Syn pathology and nigrostriatal dopaminergic degeneration remain poorly understood. Previous studies demonstrate cholesterol 24-hydroxylase (CYP46A1) increases the risk for PD. Moreover, 24-hydroxycholesterol (24-OHC), a brain-specific oxysterol that is catalyzed by CYP46A1, is elevated in the cerebrospinal fluid of PD patients. Herein, we show that the levels of CYP46A1 and 24-OHC are elevated in PD patients and increase with age in a mouse model. Overexpression of CYP46A1 intensifies α-Syn pathology, whereas genetic removal of CYP46A1 attenuates α-Syn neurotoxicity and nigrostriatal dopaminergic degeneration in the brain. Moreover, supplementation with exogenous 24-OHC exacerbates the mitochondrial dysfunction induced by α-Syn fibrils. Intracerebral injection of 24-OHC enhances the spread of α-Syn pathology and dopaminergic neurodegeneration via elevated X-box binding protein 1 (XBP1) and lymphocyte-activation gene 3 (LAG3) levels. Thus, elevated CYP46A1 and 24-OHC promote neurotoxicity and the spread of α-Syn via the XBP1‒LAG3 axis. Strategies aimed at inhibiting the CYP46A1-24-OHC axis and LAG3 could hold promise as disease-modifying therapies for PD.
Question: Write a study description for the study titled 'Plasmodium falciparum adapts its investment into replication versus transmission according to the host environment'.
Answer: The malaria parasite life cycle includes asexual replication in human blood, with a proportion of parasites differentiating to gametocytes required for transmission to mosquitoes. Commitment to differentiate into gametocytes, which is marked by activation of the parasite transcription factor ap2-g , is known to be influenced by host factors but a comprehensive model remains uncertain. Here we analyze data from 828 children in Kilifi, Kenya with severe, uncomplicated, and asymptomatic malaria infection over 18 years of falling malaria transmission. We examine markers of host immunity and metabolism, and markers of parasite growth and transmission investment. We find that inflammatory responses and reduced plasma lysophosphatidylcholine levels are associated with markers of increased investment in parasite sexual reproduction (i.e., transmission investment) and reduced growth (i.e., asexual replication). This association becomes stronger with falling transmission and suggests that parasites can rapidly respond to the within-host environment, which in turn is subject to changing transmission.
Question: Write a study description for the study titled 'Lipidomic profiling reveals distinct differences in plasma lipid composition in healthy, prediabetic and type 2 diabetic individuals'.
Answer: The relationship between dyslipidemia and type 2 diabetes mellitus (T2D) has been extensively reported, but the global lipid profiles, especially in the East Asia population, associated with the development of T2D remain to be characterized. Liquid chromatography coupled to tandem mass spectrometry was applied to detect the global lipidome in the fasting plasma of 293 Chinese individuals, including 114 T2D patients, 81 prediabetic subjects and 98 individuals with normal glucose tolerance (NGT). Both qualitative and quantitative analyses revealed a gradual change in plasma lipid features with T2D patients exhibiting characteristics close to those of prediabetic individuals, whereas they differed significantly from individuals with NGT. We constructed and validated a random forest classifier with 28 lipidomic features that effectively discriminated T2D from NGT or prediabetes. Most of the selected features significantly correlated with diabetic clinical indices. Hydroxybutyrylcarnitine was positively correlated with fasting plasma glucose, 2-hour postprandial glucose, glycated hemoglobin and insulin resistance index (HOMA-IR). Lysophosphatidylcholines such as lysophosphatidylcholine (18:0), lysophosphatidylcholine (18:1) and lysophosphatidylcholine (18:2) were all negatively correlated with HOMA-IR. The altered plasma lipidome in Chinese T2D and prediabetic subjects suggests that lipid features may play a role in the pathogenesis of T2D and that such features may provide a basis for evaluating risk and monitoring disease development.
Question: Write a study description for the study titled 'Natural variation of root exudates in Arabidopsis thaliana-linking metabolomic and genomic data'.
Answer: The 19 parent lines of the Arabidopsis thaliana MAGIC collection show significant differences in their root exudate profiles. Changes in metabolism were analyzed by ultra-performance liquid chromatography coupled to electrospray ionization quadrupole time–of–flight mass spectrometry (UPLC-ESI-QTOF-MS) untargeted in positive and negative mode, and targeted for a set of known metabolites.
Question: Write a study description for the study titled 'Comprehensive evaluation of untargeted metabolomics data processing software in feature detection, quantification and discriminating marker selection (AB SCIEX TripleTOF 6600 assay)'.
Answer: Data analysis represents a key challenge for untargeted metabolomics studies and it commonly requires extensive processing of more than thousands of metabolite peaks included in raw high-resolution MS data. Although a number of software packages have been developed to facilitate untargeted data processing, they have not been comprehensively scrutinized in the capability of feature detection, quantification and marker selection using a well-defined benchmark sample set. In this study, we acquired a benchmark dataset from standard mixtures consisting of 1100 compounds with specified concentration ratios including 130 compounds with significant variation of concentrations. Five software evaluated here (MS-Dial, MZmine 2, XCMS, MarkerView, and Compound Discoverer) showed similar performance in detection of true features derived from compounds in the mixtures. However, significant differences between untargeted metabolomics software were observed in relative quantification of true features in the benchmark dataset. MZmine 2 outperformed the other software in terms of quantification accuracy and it reported the most true discriminating markers together with the fewest false markers. Further-more, we assessed selection of discriminating markers by different software using both the benchmark dataset and a real-case metabolomics dataset to propose combined usage of two software for increasing confidence of biomarker identification. Our findings from comprehensive evaluation of untargeted metabolomics software would help guide future improvements of these widely used bioinformatics tools and enable users to properly interpret their metabolomics results.  AB SCIEX TripleTOF 6600 assay protocols and data are reported in the current study MTBLS736. Thermo Q Exactive HF assay protocols and data are reported in MTBLS733.
Question: Write a study description for the study titled 'Host autophagy mediates organ wasting and nutrient mobilization for tumor growth'.
Answer: During tumor growth-when nutrient and anabolic demands are high-autophagy supports tumor metabolism and growth through lysosomal organelle turnover and nutrient recycling. Ras-driven tumors additionally invoke non-autonomous autophagy in the microenvironment to support tumor growth, in part through transfer of amino acids. Here we uncover a third critical role of autophagy in mediating systemic organ wasting and nutrient mobilization for tumor growth using a well-characterized malignant tumor model in Drosophila melanogaster. Micro-computed X-ray tomography and metabolic profiling reveal that RasV12 ; scrib-/- tumors grow 10-fold in volume, while systemic organ wasting unfolds with progressive muscle atrophy, loss of body mass, -motility, -feeding, and eventually death. Tissue wasting is found to be mediated by autophagy and results in host mobilization of amino acids and sugars into circulation. Natural abundance Carbon 13 tracing demonstrates that tumor biomass is increasingly derived from host tissues as a nutrient source as wasting progresses. We conclude that host autophagy mediates organ wasting and nutrient mobilization that is utilized for tumor growth.
Question: Write a study description for the study titled 'The Manchurian Walnut Genome: Insights into Juglone and Lipid Biosynthesis'.
Answer: BACKGROUND: Manchurian walnut (Juglans mandshurica Maxim.) is a tree with multiple industrial uses and medicinal properties in the Juglandaceae family (walnuts and hickories). J. mandshurica produces juglone, which is a toxic allelopathic agent and has potential utilization value. Furthermore, the seed of J. mandshurica is rich in various unsaturated fatty acids and has high nutritive value.FINDINGS: Here, we present a high-quality chromosome-scale reference genome assembly and annotation for J. mandshurica (n = 16) with a contig N50 of 21.4 Mb by combining PacBio high-fidelity reads with high-throughput chromosome conformation capture data. The assembled genome has an estimated sequence size of 548.7 Mb and consists of 657 contigs, 623 scaffolds and 40,453 protein-coding genes. In total, 60.99% of the assembled genome consists of repetitive sequences. Sixteen super-scaffolds corresponding to the 16 chromosomes were assembled, with a scaffold N50 length of 33.7 Mb and a BUSCO complete gene percentage of 98.3%. J. mandshurica displays a close sequence relationship with Juglans cathayensis, with a divergence time of 13.8 million years ago. Combining the high-quality genome, transcriptome and metabolomics data, we constructed a gene-to-metabolite network and identified 566 core and conserved differentially expressed genes, which may be involved in juglone biosynthesis. Five CYP450 genes were found that may contribute to juglone accumulation. NAC, bZip, NF-YA and NF-YC are positively correlated with the juglone content. Some candidate regulators (e.g., FUS3, ABI3, LEC2 and WRI1 transcription factors) involved in the regulation of lipid biosynthesis were also identified.CONCLUSIONS: Our genomic data provide new insights into the evolution of the walnut genome and create a new platform for accelerating molecular breeding and improving the comprehensive utilization of these economically important tree species.
Question: Write a study description for the study titled 'Metabolomic Profiling of Renal Cyst Fluid in Advanced ADPKD: Insights from Dialysis and Transplantation Cohorts'.
Answer: Background: Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary disorder characterized by progressive renal cyst formation, often leading to end-stage kidney disease (ESKD). While urinary metabolomics in ADPKD has been extensively studied, the composition of renal cyst fluid, particularly in advanced stages, remains largely unexplored.Methods: We conducted a comprehensive metabolomic analysis of renal cyst fluid from 26 ADPKD patients (20 on dialysis, six with kidney transplants) using ¹H-NMR spectroscopy and mass spectrometry. Cysts were clustered based on NMR measurements, and differences were analyzed across groups defined by renal function status, cyst volume and cyst fluid sodium concentrations.Results: Metabolomic profiling revealed significant differences between cyst fluid compositions from dialysis patients and transplant recipients. Transplant recipients exhibited elevated levels of proteinogenic amino acids such as leucine, isoleucine, valine and alanine, with concentrations 2-3-fold higher than physiological serum levels. Conversely, dialysis patients had higher levels of myoinositol (334 ± 101 µM vs 108 ± 74 µM in transplant recipients), creatinine, sucrose, τ-methylhistidine, trigonelline and sarcosine. Despite intra- and interindividual variability, cyst fluid from the same patient displayed significant homogeneity. Interestingly, metabolomic profiles were not altered by cyst size.Conclusion: This first systematic metabolomic analysis of renal cyst fluid in advanced ADPKD reveals distinct metabolic signatures linked to renal function, offering new insights into cystogenesis and disease progression. Although the data were obtained from advanced-stage disease, they provide novel insights into the pathophysiology of ADPKD and highlight the potential of renal cyst fluid metabolomics for identifying biomarkers and therapeutic targets.
Question: Write a study description for the study titled 'The gut microbiome and metabolites are altered and interrelated in patients with rheumatoid arthritis'.
Answer: The relationship among the gut microbiome, global fecal metabolites and rheumatoid arthritis (RA) has not been systematically evaluated. In this study, we performed 16S rDNA sequencing and liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based nontargeted metabolomic profiling on feces of 26 untreated RA patients and 26 healthy controls. Twenty-six genera and forty-one MS2-identified metabolites were significantly altered in the RA patients. Klebsiella, Escherichia, Eisenbergiella and Flavobacterium were more abundant in the RA patients, while Fusicatenibacter, Megamonas and Enterococcus were more abundant in the healthy controls. Function prediction analysis demonstrated that the biosynthesis pathways of amino acids, such as L-arginine and aromatic amino acids, were depleted in the RA group. In the metabolome results, fecal metabolites including glycerophospholipids (PC(18:3(9Z,12Z,15Z)/16:1(9Z)), lysoPE(19:1), lysoPE(18:0), lysoPC(18:0/0:0)), sphingolipids (Cer(d18:0/16:0), Cer(d18:0/12:0), Cer(d18:0/14:0)), kynurenic acid, xanthurenic acid and 3-hydroxyanthranilic acid were remarkably altered between the RA patients and healthy controls. Dysregulation of pathways, such as tryptophan metabolism, alpha-linolenic acid metabolism and glycerophospholipid metabolism, may contribute to the development of RA. Additionally, we revealed that the gut microbiome and metabolites were interrelated in the RA patients, while Escherichia was the core genus. By depicting the overall landscape of the intestinal microbiome and metabolome in RA patients, our study could provide possible novel research directions regarding RA pathogenesis and targeted therapy.
Question: Write a study description for the study titled 'Matrix Effect on Chemical Isotope Labeling and Its Implication in Metabolomic Sample Preparation for Quantitative Metabolomics'.
Answer: Matrix effect from various constituents in biological samples can reduce the accuracy of quantitative metabolomics. Differential chemical isotope labeling liquid chromatography mass spectrometry (CIL LC-MS) can overcome the matrix effect on MS detection based on measuring the intensity ratios of metabolite peak pairs detected in a mixture of a light-isotope labeled sample and a heavy-isotope labeled reference sample. However, the chemical labeling process itself may encounter matrix effect which can influence the overall quantitative results. In this work, we report the effects of salts and buffers commonly present in metabolomic samples on dansylation labeling. It is shown that high concentrations of NaCl and phosphate buffer (>50 mM) or PBS can reduce or enhance the labeling efficiencies of metabolites. By maintaining similar matrix contents in an individual sample vs. a reference sample, relative quantification of metabolites can be performed without compromising the metabolomic profiling results. For samples containing varying amounts of high salts such as urine, we demonstrate that the matrix effect can be largely overcome by diluting the original sample before dansylation labeling (e.g., 4-fold dilution for urine).
Question: Write a study description for the study titled 'Chemical Diversity and Classification of Secondary Metabolites in Nine Bryophyte Species'.
Answer: The central aim in ecometabolomics and chemical ecology is to pinpoint chemical features that explain molecular functioning. The greatest challenge is the identification of compounds due to the lack of constitutive reference spectra, the large number of completely unknown compounds, and bioinformatic methods to analyze the big data. In this study we present an interdisciplinary methodological framework that extends ultra-performance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC/ESI-QTOF-MS) with data-dependent acquisition (DDA-MS) and the automated in silico classification of fragment peaks into compound classes. We synthesize findings from a prior study that explored the influence of seasonal variations on the chemodiversity of secondary metabolites in nine bryophyte species. Here we reuse and extend the representative dataset with DDA-MS data. Hierarchical clustering, heatmaps, dbRDA, and ANOVA with post-hoc Tukey HSD were used to determine relationships of the study factors species, seasons, and ecological characteristics. The tested bryophytes showed species-specific metabolic responses to seasonal variations (50% vs. 5% of explained variation). Marchantia polymorpha, Plagiomnium undulatum, and Polytrichum strictum were biochemically most diverse and unique. Flavonoids and sesquiterpenoids were upregulated in all bryophytes in the growing seasons. We identified ecological functioning of compound classes indicating light protection (flavonoids), biotic and pathogen interactions (sesquiterpenoids, flavonoids), low temperature and desiccation tolerance (glycosides, sesquiterpenoids, anthocyanins, lactones), and moss growth supporting anatomic structures (few methoxyphenols and cinnamic acids as part of proto-lignin constituents). The reusable bioinformatic framework of this study can differentiate species based on automated compound classification. Our study allows detailed insights into the ecological roles of biochemical constituents of bryophytes with regard to seasonal variations. We demonstrate that compound classification can be improved with adding constitutive reference spectra to existing spectral libraries. We also show that generalization on compound classes improves our understanding of molecular ecological functioning and can be used to generate new research hypotheses.