LuYuxing/MetaBench huggingface dataset:
Question: Write a study description for the study titled 'Multiple roles of extracellular vesicles in promoting microbial driven elemental cycle'.
Answer: Microbial driven manganese (Mn) reduction influences the geochemical cycling of Mn and the environmental fate of various organic and inorganic substances. Extracellular vesicles (EVs) are known to impact microbial metabolic activities, but their specific role in Mn reduction remains arcane. Here, we investigated the potential and mechanistic roles of EVs in this process by integrating metagenomic analysis of environmental EVs with functional assays in representative dissimilatory metal-reducing bacteria. Microbial physiological assays and in situ electrochemical analyses revealed that the addition of EVs enhanced cellular metabolism, promoted biofilm formation, and facilitated extracellular electron transfer. The presence of various redox enzymes and metabolites in EVs contributed to more efficient substrate utilization and energy conservation. The electron transfer-promoting effect of EVs is primarily attributed to OmcA/MtrC, CymA, and FMN. These findings highlight the multifaceted role of EVs in microbial Mn reduction and suggest their broader involvement in elemental cycling and pollutant degradation.
Question: Write a study description for the study titled 'Flint glass bottles cause white wine aroma identity degradation'.
Answer: Due to marketing recommendations, white wines are often bottled in flint glass to improve aesthetics and showcase wine color. Although this practice is known to cause a wine fault, the influence of light on the fruity and flowery aromatic profile of wine is unknown. The aim of this study was to investigate the changes to the white wine volatilome under typical supermarket shelf conditions, using 1,052 bottles of 24 white wines. After only 7 d of shelf life in flint glass bottles, a dramatic loss in terpenes (10 to 30%) and norisoprenoids (30 to 70%) was recorded, whereas colored glass bottles did not evidence such behavior even after 50 d, and darkness preserved the wine's fruity and flowery aromatic integrity. We also proposed an alternative mechanism for the insurgence of the lightstrike off-odor, which takes the varietal aroma loss into account. In light of this understanding of the flint glass negative impact on white wine aroma identity and sensorial character, this packaging should be strongly discouraged. The same findings should be valid for a wide range of several daily consumed foodstuff where transparent packaging is used.
Question: Write a study description for the study titled 'Lipid Data Analyzer: Decision rule set development by lipid standards of known constituent fatty acyl and/or alkyl/1-alkenyl chains and their respective sn-positions (Control experiment 1)'.
Answer: Lipid Data Analyzer (LDA; http://genome.tugraz.at/lda2) provides automated and reliable annotation of lipid species and their molecular structures in high-throughput data from chromatography-coupled tandem mass spectrometry using embedded rule sets. Using various low- and high-resolution mass spectrometry instruments with several collision energies, the method's platform independence is proved. The software's reliability, flexibility, and ability to identify novel lipid molecular species may now render current state-of-the-art lipid libraries obsolete.The basic fragment rules are based on published results. From the experimental data, the rules were adapted and extended by visual inspection of spectra. Detectable fragments, mandatory fragment derived intensity rules, and extracted decisive differences for many isobaric subclasses/adducts were all identified. In addition, intensity relationships characteristic for sn-position assignment were determined.Control experiment 1 assays can be found in the current study MTBLS394.Control experiment 2 assays can be found in study MTBLS391.Control experiment 3 assays can be found in study MTBLS398.Murine liver lipidome experiment assays can be found in study MTBLS396.LipidBlast benchmarking assays can be found in study MTBLS397.HCD characterization and regioisomer detection assays can be found in study MTBLS462.
Question: Write a study description for the study titled 'Metabolic mapping of the human solute carrier superfamily'.
Answer: Solute carrier (SLC) transporters govern most of the chemical exchange across cellular membranes and are integral to metabolic regulation, which in turn is linked to cellular function and identity. Despite their key role, individual functions of the SLC superfamily members were not evaluated systematically. We determined the metabolic and transcriptional profiles upon SLC overexpression in knock-out or wild-type isogenic cell backgrounds for 378 SLCs and 441 SLCs, respectively. Targeted metabolomics provided a fingerprint of 189 intracellular metabolites, while transcriptomics offered insights into cellular programs modulated by SLC expression. Beyond the metabolic profiles of 102 SLCs directly related to their known substrates, we identified putative substrates or metabolic pathway connections for 71 SLCs without previously annotated bona fide substrates, including SLC45A4 as a new polyamine transporter. By comparing the molecular profiles, we identified functionally related SLC groups, including some with distinct impacts on osmolyte balancing and glycosylation. This MetaboLights study deposits LC-MS data from ad-hoc targeted metabolite measurements for deorphanization of SLC45A4 and validation of an osmolyte balancing response identified in one of the transcriptomic clusters.
Question: Write a study description for the study titled 'Mitochondrial respiration controls neoangiogenesis during wound healing and tumour growth'.
Answer: The vasculature represents a highly plastic compartment, capable of switching from a quiescent to an active proliferative state during angiogenesis. Metabolic reprogramming in endothelial cells (ECs) thereby is crucial to cover the increasing cellular energy demand under growth conditions. Here we assess the impact of mitochondrial bioenergetics on neovascularisation, by deleting cox10 gene encoding an assembly factor of cytochrome c oxidase (COX) specifically in mouse ECs, providing a model for vasculature-restricted respiratory deficiency. We show that EC-specific cox10 ablation results in deficient vascular development causing embryonic lethality. In adult mice induction of EC-specific cox10 gene deletion produces no overt phenotype. However, the angiogenic capacity of COX-deficient ECs is severely compromised under energetically demanding conditions, as revealed by significantly delayed wound-healing and impaired tumour growth. We provide genetic evidence for a requirement of mitochondrial respiration in vascular endothelial cells for neoangiogenesis during development, tissue repair and cancer.
Question: Write a study description for the study titled 'Integrating genomics and multi‐platform metabolomics enables metabolite QTL detection in breeding‐relevant apple germplasm'.
Answer: Apple (Malus × domestica) has commercial and nutritional value, but breeding constraints of tree crops limit varietal improvement. Marker-assisted selection minimizes these drawbacks, but breeders lack applications for targeting fruit phytochemicals. To understand genotype-phytochemical associations in apples, we have developed a high-throughput integration strategy for genomic and multi-platform metabolomics data. 124 apple genotypes, including members of three pedigree-connected breeding families alongside diverse cultivars and wild selections, were genotyped and phenotyped. Metabolite genome-wide association studies (mGWAS) were conducted with ~10,000 single nucleotide polymorphisms and phenotypic data acquired via LC-MS and 1 H NMR untargeted metabolomics. Putative metabolite quantitative trait loci (mQTL) were then validated via pedigree-based analyses (PBA). Using our developed method, 519, 726, and 177 putative mQTL were detected in LC-MS positive and negative ionization modes and NMR, respectively. mQTL were indicated on each chromosome, with hotspots on linkage groups 16 and 17. A chlorogenic acid mQTL was discovered on chromosome 17 via mGWAS and validated with a two-step PBA, enabling discovery of novel candidate gene-metabolite relationships. Complementary data from three metabolomics approaches and dual genomics analyses increased confidence in validity of compound annotation and mQTL detection. Our platform demonstrates the utility of multi-omic integration to advance data-driven, phytochemical-based plant breeding.
Question: Write a study description for the study titled 'Metabolomics and lipidomics reveal perturbation of sphingolipid metabolism by a novel anti-trypanosomal 3-(oxazolo[4,5-b]pyridine-2-yl)anilide'.
Answer: Trypanosoma brucei is the causative agent of human African trypanosomiasis, which is responsible for thousands of deaths every year. Current therapies are limited and there is an urgent need to develop new drugs. The anti-trypanosomal compound, 3-(oxazolo[4,5-b]pyridine-2-yl)anilide (OXPA), was initially identified in a phenotypic screen and subsequently optimized by structure–activity directed medicinal chemistry. It has been shown to be non-toxic and to be active against a number of trypanosomatid parasites. However, nothing is known about its mechanism of action.
Question: Write a study description for the study titled 'OVCAR-3 spheroid-derived cells display distinct metabolic profiles'.
Answer: Recently, multicellular spheroids were isolated from a well-established epithelial ovarian cancer cell line, OVCAR-3, and were propagated in vitro. These spheroid derived cells displayed numerous hallmarks of cancer stem cells, which are chemo and radioresistant cells thought to be a significant cause of cancer recurrence and resultant mortality. Gene set enrichment analysis of expression data from the OVCAR-3 cells and the spheroid-derived putative cancer stem cells identified several metabolic pathways enriched in differentially expressed genes. Before this, there had been little previous knowledge or investigation of systems-scale metabolic differences between cancer cells and cancer stem cells, and no knowledge of such differences in ovarian cancer stem cells. To determine if there were substantial metabolic changes corresponding with these transcriptional differences, we used two-dimensional gas chromatography coupled to mass spectrometry to measure the metabolite profiles of the two cell lines. These two cell lines exhibited significant metabolic differences in both intracellular and extracellular metabolite measurements. Principal components analysis, an unsupervised dimensional reduction technique, showed complete separation between the two cell types based on their metabolite profiles. Pathway analysis of intracellular metabolomics data revealed close overlap with metabolic pathways identified from gene expression data, with four out of six pathways found enriched in gene-level analysis also enriched in metabolite-level analysis. Some of those pathways contained multiple metabolites that were individually statistically significantly different between the two cell lines, with one of the most broadly and consistently different pathways, arginine and proline metabolism, suggesting an interesting hypothesis about cancerous and stem-like metabolic phenotypes in this pair of cell lines. Overall, we demonstrate for the first time that metabolism in an ovarian cancer stem cell line is distinct from that of more differentiated isogenic cancer cells, supporting the potential importance of metabolism in the differences between cancer cells and cancer stem cells.
Question: Write a study description for the study titled 'MaHPIC Experiment 30: Metabolomics from the pilot experiment for Macaca mulatta infected with Plasmodium knowlesi Malayan strain sporozoites to produce and integrate clinical, hematological, parasitological, omics, telemetric and histopathological measures of acute primary infection'.
Answer: Telemetry devices (DSI, model L11) with blood pressure sensors and electrocardiogram (ECG) leads were surgically implanted in two malaria-naive male rhesus macaques (Macaca mulatta), approximately three years of age. After a resting period of two weeks, physiological data that include activity, temperature, ECG, and blood pressure were continuously collected. Two weeks after activation of the telemetry implant, the macaques were inoculated intravenously with cryopreserved P. knowlesi Malayan strain salivary gland sporozoites, obtained from Anopheles dirus infected with parasites from the Pk1A+ clone. The P. knowlesi sporozoites were produced, isolated and cryopreserved at the Centers for Disease Control and Prevention. After inoculation, the macaques were profiled for clinical, hematological, parasitological, immunological, functional genomic, lipidomic, proteomic, metabolomic, telemetric and histopathological measurements. The experiment was designed for pathology studies, with terminal necropsies on days 11 (RKy15) or 19 (Red16). The anti-malarial drug artemether was subcuratively administered selectively to one subject (REd16) during the primary parasitemia to suppress clinical complications. Capillary blood samples were collected daily for the measurement of complete blood counts, reticulocytes, and parasitemias. Capillary blood samples were collected every other day to obtain plasma for metabolomic analysis. Venous blood and bone marrow samples were collected at five timepoints for functional genomic, proteomic, lipidomic, and immunological analyses. Physiological data were continuously captured via telemetry. Within the MaHPIC, this project is known as 'Experiment 30'. This dataset was produced by Dean Jones at Emory University. To access other publicly available results from 'E30' and other MaHPIC Experiments, including clinical results (specifics on drugs administered, diet, and veterinary interventions), and other omics, visit http://plasmodb.org/plasmo/mahpic.jsp. This page will be updated as datasets are released to the public. The experimental design and protocols for this study were approved by the Emory University Institutional Animal Care and Use Committee (IACUC) and the MRMC Office of Research Protection Animal Care and Use Review Office (ACURO). Linked Studies: Malaria Host-Pathogen Interaction Center (MaHPIC)
Question: Write a study description for the study titled 'Changes in Amino Acid and Acylcarnitine Plasma Profiles for Distinguishing Patients with Multiple Sclerosis from Healthy Controls'.
Answer: McDonald criteria and magnetic resonance imaging (MRI) are used for the diagnosis of multiple sclerosis (MS); nevertheless, it takes a considerable amount of time to make a clinical decision. Amino acid and fatty acid metabolic pathways are disturbed in MS, and this information could be useful for diagnosis. The aim of our study was to find changes in amino acid and acylcarnitine plasma profiles for distinguishing patients with multiple sclerosis from healthy controls. We have applied a targeted metabolomics approach based on tandem mass-spectrometric analysis of amino acids and acylcarnitines in dried plasma spots followed by multivariate statistical analysis for discovery of differences between MS (n = 16) and control (n = 12) groups. It was found that partial least square discriminant analysis yielded better group classification as compared to principal component linear discriminant analysis and the random forest algorithm. All the three models detected noticeable changes in the amino acid and acylcarnitine profiles in the MS group relative to the control group. Our results hold promise for further development of the clinical decision support system.
Question: Write a study description for the study titled 'RespectM revealed metabolic heterogeneity powers deep learning for reshaping the DBTL cycle'.
Answer: Synthetic biology, relying on Design-Build-Test-Learn (DBTL) cycle, aims to solve medicine, manufacturing and agriculture problems. However, the DBTL cycle’s Learn (L) step lacks predictive power for the behavior of biological systems, resulting from the incompatibility between sparse testing data and chaotic metabolic networks. Herein, we develop a method, 'RespectM', based on mass spectrometry imaging, which is able to detect metabolites at a rate of 500 cells per hour with high efficiency. In this study, 4321 single cell level metabolomics data were acquired, representing metabolic heterogeneity. An optimizable deep neural network was applied to learn from metabolic heterogeneity and a 'heterogeneity-powered learning (HPL)' based model was trained as well. By testing the HPL based model, we suggest minimal operations to achieve high triglyceride production for engineering. The HPL strategy could revolutionize rational design and reshape the DBTL cycle.
Question: Write a study description for the study titled 'The killing mechanism of teixobactin against methicillin-resistant Staphylococcus aureus (MRSA): An untargeted metabolomics study'.
Answer: The discovery of antibiotics has led to the effective treatment of bacterial infections that were otherwise fatal and has had a transformative effect on modern medicine. Teixobactin is an unusual depsipeptide natural product that was recently discovered from a previously unculturable soil bacterium which is active against several Gram-positive pathogens, including methicillin- resistant Staphylococcus aureus and vancomycin-resistant Enterococci. One of the key attractive features of teixobactin as an antibiotic lead is that resistance could not be generated in a laboratory setting against S. aureus. This is proposed to be a result of the mechanism of action that involves binding to essential bacterial cell wall synthesis building blocks lipid II and lipid III.In the present study, metabolomics was used to investigate the potential metabolic pathways and mode of action involved in mechanisms of antibacterial activity and bacterial killing of the synthetic teixobactin analog Leu10-teixobactin against an MRSA strain, S. aureus ATCC700699. The metabolomes of S. aureus ATCC700699 cells were compared at 1, 3 and 6 h following treatment with Leu10-teixobactin (0.5 µg/ml, i.e. 0.5x MIC) and the untreated controls. Leu10-teixobactin significantly perturbed bacterial membrane lipids (glycerophospholipids and fatty acids), peptidoglycan (lipid I and II) metabolism and cell wall teichoic acid (lipid III) biosynthesis as early as after 1 h of treatment reflecting an initial activity on the cell envelope. Concordant with its time-dependent antibacterial killing action, Leu10-teixobactin caused more perturbations in the levels of key intermediates in pathways of amino-sugar and nucleotide-sugar metabolism and their downstream peptidoglycan and teichoic acid biosynthesis at 3 and 6 h. Significant perturbations in arginine metabolism and interrelated tricarboxylic acid cycle, histidine metabolism, pantothenate and Coenzyme A biosynthesis were also observed at 3 and 6 h.To conclude, this is the first study to provide novel metabolomics mechanistic information which lends to support the development of teixobactin as an antibacterial drug for the treatment of multi-drug resistant Gram-positive infections.
Question: Write a study description for the study titled 'Geographic variation of mutagenic exposures in kidney cancer genomes'.
Answer: International differences in the incidence of many cancer types indicate the existence of carcinogen exposures that have not been identified by conventional epidemiology yet potentially make a substantial contribution to cancer burden1. This pertains to clear cell renal cell carcinoma (ccRCC), for which obesity, hypertension, and tobacco smoking are risk factors but do not explain its geographical variation in incidence2. Some carcinogens generate somatic mutations and a complementary strategy for detecting past exposures is to sequence the genomes of cancers from populations with different incidence rates and infer underlying causes from differences in patterns of somatic mutations. Here, we sequenced 962 ccRCC from 11 countries of varying incidence. Somatic mutation profiles differed between countries. In Romania, Serbia and Thailand, mutational signatures likely caused by extracts of Aristolochia plants were present in most cases and rare elsewhere. In Japan, a mutational signature of unknown cause was found in >70% cases and <2% elsewhere. A further mutational signature of unknown cause was ubiquitous but exhibited higher mutation loads in countries with higher kidney cancer incidence rates (p-value <6 × 10−18). Known signatures of tobacco smoking correlated with tobacco consumption, but no signature was associated with obesity or hypertension suggesting non-mutagenic mechanisms of action underlying these risk factors. The results indicate the existence of multiple, geographically variable, mutagenic exposures potentially affecting 10s of millions of people and illustrate the opportunities for new insights into cancer causation through large-scale global cancer genomics.Linked cross omic data sets:Geographic variation of mutagenic exposures in kidney cancer genomes – patient metadata files (Mutographs) associated with this study are available in the European Genome-Phenome Archive: https://ega-archive.org/datasets/EGAD00001012223.
Question: Write a study description for the study titled 'IAPP toxicity activates HIF1α/PFKFB3 signaling delaying β-cell loss at the expense of β-cell function'.
Answer: The islet in type 2 diabetes (T2D) is characterized by amyloid deposits derived from islet amyloid polypeptide (IAPP), a protein co-expressed with insulin by β-cells. In common with amyloidogenic proteins implicated in neurodegeneration, human IAPP (hIAPP) forms membrane permeant toxic oligomers implicated in misfolded protein stress. Here, we establish that hIAPP misfolded protein stress activates HIF1α/PFKFB3 signaling, this increases glycolysis disengaged from oxidative phosphorylation with mitochondrial fragmentation and perinuclear clustering, considered a protective posture against increased cytosolic Ca2+ characteristic of toxic oligomer stress. In contrast to tissues with the capacity to regenerate, β-cells in adult humans are minimally replicative, and therefore fail to execute the second pro-regenerative phase of the HIF1α/PFKFB3 injury pathway. Instead, β-cells in T2D remain trapped in the pro-survival first phase of the HIF1α injury repair response with metabolism and the mitochondrial network adapted to slow the rate of cell attrition at the expense of β-cell function.