LuYuxing/MetaBench huggingface dataset:
Question: Write a study description for the study titled 'First-in-class MKK4 inhibitors enhance liver regeneration and prevent liver failure'.
Answer: Diminished hepatocyte regeneration is a key feature of acute and chronic liver diseases and after extended liver resections, resulting in the inability to maintain or restore a sufficient functional liver mass. Therapies to restore hepatocyte regeneration are lacking, making liver transplantation the only curative option for end-stage liver disease. Here, we report on the structure-based development and characterization (nuclear magnetic resonance [NMR] spectroscopy) of first-in-class small molecule inhibitors of the dual-specificity kinase MKK4 (MKK4i). MKK4i increased liver regeneration upon hepatectomy in murine and porcine models, allowed for survival of pigs in a lethal 85% hepatectomy model, and showed antisteatotic and antifibrotic effects in liver disease mouse models. A first-in-human phase I trial (European Union Drug Regulating Authorities Clinical Trials [EudraCT] 2021-000193-28) with the clinical candidate HRX215 was conducted and revealed excellent safety and pharmacokinetics. Clinical trials to probe HRX215 for prevention/treatment of liver failure after extensive oncological liver resections or after transplantation of small grafts are warranted.
Question: Write a study description for the study titled 'Functional Metabolomics Describes the Yeast Biosynthetic Regulome'.
Answer: Genome-metabolism interactions enable cell growth. To probe the extent of these interactions and delineate their functional contributions, we quantified the Saccharomyces amino acid metabolome and its response to systematic gene deletion. Over one-third of coding genes, in particular those important for chromatin dynamics, translation, and transport, contribute to biosynthetic metabolism. Specific amino acid signatures characterize genes of similar function. This enabled us to exploit functional metabolomics to connect metabolic regulators to their effectors, as exemplified by TORC1, whose inhibition in exponentially growing cells is shown to match an interruption in endomembrane transport. Providing orthogonal information compared to physical and genetic interaction networks, metabolomic signatures cluster more than half of the so far uncharacterized yeast genes and provide functional annotation for them. A major part of coding genes is therefore participating in gene-metabolism interactions that expose the metabolism regulatory network and enable access to an underexplored space in gene function.
Question: Write a study description for the study titled 'Metabolic reaction network-based recursive metabolite annotation for untargeted metabolomics (Aging mouse liver negative mode)'.
Answer: Large-scale metabolite annotation is a challenge in liquid chromatogram-mass spectrometry (LC-MS)-based untargeted metabolomics. Here, we develop a metabolic reaction network (MRN)-based recursive algorithm (MetDNA) that expands metabolite annotations without the need for a comprehensive standard spectral library. MetDNA is based on the rationale that seed metabolites and their reaction-paired neighbors tend to share structural similarities resulting in similar MS2 spectra. MetDNA characterizes initial seed metabolites using a small library of MS2 spectra, and utilizes their experimental MS2 spectra as surrogate spectra to annotate their reaction-paired neighbor metabolites, which subsequently serve as the basis for recursive analysis. Using different LC-MS platforms, data acquisition methods, and biological samples, we showcase the utility and versatility of MetDNA and demonstrate that about 2000 metabolites can cumulatively be annotated from one experiment. Our results demonstrate that MetDNA substantially expands metabolite annotation, enabling quantitative assessment of metabolic pathways and facilitating integrative multi-omics analysis.Aging mouse liver positive mode is reported in MTBLS601.Aging mouse liver negative mode is reported in MTBLS606.Aging fruit fly positive mode is reported in MTBLS612.Aging fruit fly negative mode is reported in MTBLS615.
Question: Write a study description for the study titled 'Mass spectrometry imaging as an emerging tool for studying metabolism in human brain organoids'.
Answer: Human brain organoids are emerging models to study human brain development and pathology as they recapitulate the development and characteristics of major neural cell types, and enable manipulation through an in vitro system. Over the past decade, with the advent of spatial technologies, mass spectrometry imaging (MSI) has become a prominent tool for metabolic microscopy, providing label-free, non-targeted molecular and spatial distribution information of the metabolites within tissue, including lipids. This technology has never been used for studies of brain organoids and here, we set out to develop a standardized protocol for preparation and mass spectrometry imaging of human brain organoids. We present an optimized and validated sample preparation protocol, including sample fixation, optimal embedding solution, homogenous deposition of matrices, data acquisition and processing to maximize the molecular information derived from mass spectrometry imaging. We focus on lipids in organoids, as they play critical roles during cellular and brain development. Using high spatial and mass resolution in positive- and negative-ion modes, we detected 260 lipids in the organoids. Seven of them were uniquely localized within the neurogenic niches or rosettes as confirmed by histology, suggesting their importance for neuroprogenitor proliferation. We observed a particularly striking distribution of ceramide-phosphoethanolamine CerPE 36:1; O2 restricted within rosettes and of phosphatidyl-ethanolamine PE 38:3, which was distributed throughout the organoid tissue but not in rosettes. This suggests that ceramide in this particular lipid species might be important for neuroprogenitor biology, while its removal may be important for terminal differentiation of their progeny. Overall, our study establishes the first optimized experimental pipeline and data processing strategy for mass spectrometry imaging of human brain organoids, allowing direct comparison of lipid signal intensities and distributions in these tissues. Further, our data shed new light on the complex processes that govern brain development by identifying specific lipid signatures that may play a role in metabolic cell fate trajectories. mass spectrometry imaging thus has great potential in advancing our understanding of early brain development as well as disease modeling and drug discovery.
Question: Write a study description for the study titled 'Umbilical cord blood metabolome differs in relation to delivery mode, birth order and sex, maternal diet and possibly future allergy development in rural children'.
Answer: Allergy is one of the most common diseases among young children yet all factors that affect development of allergy remain unclear. In a small cohort of 65 children living in the same rural area of south-west Sweden, we have previously found that maternal factors, including prenatal diet, affect childhood allergy risk, suggesting that in utero conditions may be important for allergy development. Here, we studied if metabolites in the umbilical cord blood of newborns may be related to development of childhood allergy, accounting for key perinatal factors such as mode of delivery, birth order and sex. Available umbilical cord blood plasma samples from 44 of the participants were analysed using gas chromatography-mass spectrometry metabolomics; allergy was diagnosed by specialised paediatricians at ages 18 months, 3 years and 8 years and included eczema, asthma, food allergy and allergic rhinoconjunctivitis. Nineteen cord blood metabolites were related to future allergy diagnosis though there was no clear pattern of up- or downregulation of metabolic pathways. In contrast, perinatal factors birth order, sex and mode of delivery affected several energy and biosynthetic pathways, including glutamate and aspartic acid-histidine metabolism (p = 0.004) and the tricarboxylic acid cycle (p = 0.006) for birth order; branched chain amino acid metabolism (p = 0.0009) and vitamin B6 metabolism (p = 0.01) for sex; and glyoxylate and dicarboxylic acid metabolism (p = 0.005) for mode of delivery. Maternal diet was also related to some of the metabolites associated with allergy. In conclusion, the cord blood metabolome includes individual metabolites that reflect lifestyle, microbial and other factors that may be associated with future allergy diagnosis, and also reflects temporally close events/factors. Larger studies are required to confirm these associations, and perinatal factors such as birth order or siblings must be considered in future cord-blood metabolome studies.
Question: Write a study description for the study titled 'Ecophysiological Study of Paraburkholderia sp. Strain 1N under Soil Solution Conditions: Dynamic Substrate Preferences and Characterization of Carbon Use Efficiency'.
Answer: We used time-resolved metabolic footprinting, an important technical approach used to monitor changes in extracellular compound concentrations during microbial growth, to study the order of substrate utilization (i.e., substrate preferences) and kinetics of a fast-growing soil isolate, Paraburkholderia sp. strain 1N. The growth of Paraburkholderia sp. 1N was monitored under aerobic conditions in a soil-extracted solubilized organic matter medium, representing a realistic diversity of available substrates and gradient of initial concentrations. We combined multiple analytical approaches to track over 150 compounds in the medium and complemented this with bulk carbon and nitrogen measurements, allowing estimates of carbon use efficiency throughout the growth curve. Targeted methods allowed the quantification of common low-molecular-weight substrates: glucose, 20 amino acids, and 9 organic acids. All targeted compounds were depleted from the medium, and depletion followed a sigmoidal curve where sufficient data were available. Substrates were utilized in at least three distinct temporal clusters as Paraburkholderia sp. 1N produced biomass at a cumulative carbon use efficiency of 0.43. The two substrates with highest initial concentrations, glucose and valine, exhibited longer usage windows, at higher biomass-normalized rates, and later in the growth curve. Contrary to hypotheses based on previous studies, we found no clear relationship between substrate nominal oxidation state of carbon (NOSC) or maximal growth rate and the order of substrate depletion. Under soil solution conditions, the growth of Paraburkholderia sp. 1N induced multiauxic substrate depletion patterns that could not be explained by the traditional paradigm of catabolite repression.IMPORTANCE: Exometabolomic footprinting methods have the capability to provide time-resolved observations of the uptake and release of hundreds of compounds during microbial growth. Of particular interest is microbial phenotyping under environmentally relevant soil conditions, consisting of relatively low concentrations and modeling pulse input events. Here, we show that growth of a bacterial soil isolate, Paraburkholderia sp. 1N, on a dilute soil extract resulted in a multiauxic metabolic response, characterized by discrete temporal clusters of substrate depletion and metabolite production. Our data did not support the hypothesis that compounds with lower energy content are used preferentially, as each cluster contained compounds with a range of nominal oxidation states of carbon. These new findings with Paraburkholderia sp. 1N, which belongs to a metabolically diverse genus, provide insights on ecological strategies employed by aerobic heterotrophs competing for low-molecular-weight substrates in soil solution.
Question: Write a study description for the study titled 'Deep functional analysis of synII, a 770 kb synthetic yeast chromosome'.
Answer: Here we report the design, construction and characterization of a 770 Kb synthetic yeast chromosome II (synII). With the UPLC-MS method, we demonstrated synII maintains a nearly wild-type phenotype and fitness despite hundreds of designer editing to it. Our phenomics, transcriptomics, proteomics data futher supports the identity of synII and wild one.
Question: Write a study description for the study titled 'Plasma metabolome alteration in dairy cows with left displaced abomasum before and after surgical correction'.
Answer: Left displaced abomasum (LDA) leads to substantial changes in the metabolism of dairy cows. Surgical correction of LDA can rapidly improve the health of cows; however, changes in metabolism following surgery are rarely described. To investigate the changes of plasma metabolome in cows with LDA before and after surgical correction, blood samples were collected from 10 healthy postpartum cows and 10 cows with LDA on the day of diagnosis, then again from the LDA cows 14 d after surgery. Serum nonesterified fatty acid, β-hydroxybutyric acid, cortisol and histamine concentration, and antioxidant enzyme (superoxide dismutase and glutathione peroxidase) activities were evaluated, and the metabolic profile in plasma was analyzed using ultra-high-performance liquid chromatography time-of-flight mass spectrometry. The results demonstrated that cows with LDA experienced severe negative energy balance and oxidative stress, which can be improved by surgical correction. The metabolic profile was analyzed using multidimensional and univariate statistical analyses, and different metabolites were identified. In total, 102 metabolites differed between cows with LDA and healthy cows. After surgical correction, 65 metabolites changed in cows with LDA, compared with these cows during the LDA event. Following surgical correction, AA levels tended to increase, and lipid levels tended to decrease in cows with LDA. Pathway analysis indicated marked changes in linoleic acid metabolism, Arg biosynthesis, and Gly, Ser, and Thr metabolism in cows at the onset of LDA and following surgical correction. Surgical treatment reversed the changes in AA and lipid metabolism in cows with LDA.
Question: Write a study description for the study titled 'Multi-Omics and Integrated Network Analyses Reveal New Insights into the Systems Relationships between Metabolites, Structural Genes, and Transcriptional Regulators in Developing Grape Berries (Vitis vinifera L.) Exposed to Water Deficit (Phenolics; UPLC-MS/MS assay)'.
Answer: Grapes are one of the major fruit crops and they are cultivated in many dry environments. This study comprehensively characterizes the metabolic response of grape berries exposed to water deficit at different developmental stages. Increases of proline, branched-chain amino acids, phenylpropanoids, anthocyanins, and free volatile organic compounds have been previously observed in grape berries exposed to water deficit. Integrating RNA-sequencing analysis of the transcriptome with large-scale analysis of central and specialized metabolites, we reveal that these increases occur via a coordinated regulation of key structural pathway genes. Water deficit-induced up-regulation of flavonoid genes is also coordinated with the down-regulation of many stilbene synthases and a consistent decrease in stilbenoid concentration. Water deficit activated both ABA-dependent and ABA-independent signal transduction pathways by modulating the expression of several transcription factors. Gene-gene and gene-metabolite network analyses showed that water deficit-responsive transcription factors such as bZIPs, AP2/ERFs, MYBs, and NACs are implicated in the regulation of stress-responsive metabolites. Enrichment of known and novel cis-regulatory elements in the promoters of several ripening-specific/water deficit-induced modules further affirms the involvement of a transcription factor cross-talk in the berry response to water deficit. Together, our integrated approaches show that water deficit-regulated gene modules are strongly linked to key fruit-quality metabolites and multiple signal transduction pathways may be critical to achieve a balance between the regulation of the stress-response and the berry ripening program. This study constitutes an invaluable resource for future discoveries and comparative studies, in grapes and other fruits, centered on reproductive tissue metabolism under abiotic stress.UPLC-MS/MS assay of Phenolics is reported in the current study MTBLS898SPME-GC-MS assay of Volatile organic compounds is reported in MTBLS982UPLC-DAD assay of Carotenoids is reported in MTBLS984
Question: Write a study description for the study titled 'Modulating the developing gut microbiota with 2’-fucosyllactose and pooled human milk oligosaccharides'.
Answer: Synthetic human milk oligosaccharide (HMO) structures are used to supplement infant formula despite limited understanding of their impact on the developing gut microbiota. Here, we assess the impact of 2-fucosyllactose (2’FL) and pooled (p)HMOs on the composition and activity of cultured microbial communities derived from seven infants. Bacterial isolates spanning 157 species were derived from these communities and individually evaluated for their responses to HMOs. Exposure to pHMOs resulted in shifts in the composition and metabolic output of the communities, including increased absolute abundance of several genera, notably Bacteroides, and production of health-associated metabolites. In contrast, the addition of 2’FL alone had no measurable effect. Over 100 non-Bifidobacterium species showed enhanced growth with pHMOs treatment, and a high degree of intraspecies variation in HMO metabolism was noted. Our study warrants further investigation into the significance of incorporating 2’FL alone into infant formula, especially in the context of gut microbiota modulation.
Question: Write a study description for the study titled 'The molecular basis for acetylhistidine synthesis by HisAT/NAT16'.
Answer: Acetylhistidine has been detected in human blood, but its origin and function are not known. It is formed when the acetyl group of acetyl-CoA is transferred to the α-amino group of histidine. Here we identify the intracellular NAT16 as the human histidine acetyltransferase (HisAT) responsible for histidine acetylation in vitro and in vivo. A NAT16 variant (p.Phe63Ser) present in >5% of the population was previously found to correlate with reduced plasma levels of acetylhistidine and increased risk of kidney disease. Our biochemical analysis of HisAT/NAT16 Phe63Ser shows reduced affinity for Histidine supporting a model where this variant has less acetylhistidine catalysis leading to lower blood level of acetylhistidine. We find that HisAT adopts a double-GNAT (Gcn5-related N-Acetyltransferase) fold where the N-terminal domain binds acetyl-CoA and with unique active site conformation allowing the binding of histidine in between the two domains. We detected similar structures from across living organisms and found that the HisAT structure is conserved in several archaeal and bacterial species. In sum, NAT16 is the human histidine acetyltransferase utilizing a rare double GNAT structure to steer plasma acetylhistidine levels with potential impact for kidney function.
Question: Write a study description for the study titled 'Recombinant Production of Biliverdin IXβ and δ Isomers in the T7 Promoter Compatible Escherichia coli Nissle'.
Answer: The ability to obtain purified biliverdin IX (BVIX) isomers other than the commercially available BVIXα is limited due to the low yields obtained by the chemical coupled oxidation of heme. Chemical oxidation requires toxic chemicals, has very poor BVIX yields (300-fold when compared to the chemical oxidation of heme.
Question: Write a study description for the study titled 'Model-driven multi-omic data analysis elucidates metabolic immunomodulators of macrophage activation'.
Answer: Macrophages are central players in immune response, manifesting divergent phenotypes to control inflammation and innate immunity through release of cytokines and other signaling factors. Recently, the focus on metabolism has been reemphasized as critical signaling and regulatory pathways of human pathophysiology, ranging from cancer to aging, often converge on metabolic responses. Here, we used genome-scale modeling and multi-omics (transcriptomics, proteomics, and metabolomics) analysis to assess metabolic features that are critical for macrophage activation. A genome-scale metabolic network for the RAW 264.7 cell line was constructed to determine metabolic modulators of activation. Metabolites well-known to be associated with immunoactivation (glucose and arginine) and immunosuppression (tryptophan and vitamin D3) were among the most critical effectors. Intracellular metabolic mechanisms were assessed, identifying a suppressive role for de-novo nucleotide synthesis. Finally, underlying metabolic mechanisms of macrophage activation were identified by analyzing multi-omic data obtained from LPS-stimulated RAW cells in the context of our flux-based predictions. This study demonstrates that the role of metabolism in regulating activation may be greater than previously anticipated and elucidates underlying connections between activation and metabolic effectors. This submission corresponds to the metabolomics data from this study.
Question: Write a study description for the study titled 'Bioinspired Rhamnolipid Protects Wheat Against Zymoseptoria tritici Through Mainly Direct Antifungal Activity and Without Major Impact on Leaf Physiology'.
Answer: Rhamnolipids (RLs), glycolipids biosynthesized by the Pseudomonas and Burkholderia genera, are known to display various activities against a wide range of pathogens. Most previous studies on RLs focused on their direct antimicrobial activity, while only a few reports described the mechanisms by which RLs induce resistance against phytopathogens and the related fitness cost on plant physiology. Here, we combined transcriptomic and metabolomic approaches to unravel the mechanisms underlying RL-induced resistance in wheat against the hemibiotrophic fungus Zymoseptoria tritici, a major pathogen of this crop. Investigations were carried out by treating wheat plants with a bioinspired synthetic mono-RL with a 12-carbon fatty acid tail, dodecanoyl α/β-L-rhamnopyranoside (Rh-Est-C12), under both infectious and non-infectious conditions to examine its potential wheat defense-eliciting and priming bioactivities. Whereas, Rh-Est-C12 conferred to wheat a significant protection against Z. tritici (41% disease severity reduction), only a slight effect of this RL on wheat leaf gene expression and metabolite accumulation was observed. A subset of 24 differentially expressed genes (DEGs) and 11 differentially accumulated metabolites (DAMs) was scored in elicitation modalities 2, 5 and 15 days post-treatment (dpt), and 25 DEGs and 17 DAMs were recorded in priming modalities 5 and 15 dpt. Most changes were down-regulations, and only a few DEGs and DAMs associated with resistance to pathogens were identified. Nevertheless, a transient early regulation in gene expression was highlighted at 2 dpt (e.g., genes involved in signaling, transcription, translation, cell-wall structure and function), suggesting a perception of the RL by the plant upon treatment. Further in vitro and in planta bioassays showed that Rh-Est-C12 displays a significant direct antimicrobial activity toward Z. tritici. Taken together, our results suggest that Rh-Est-C12 confers protection to wheat against Z. tritici through direct antifungal activity and, to a lesser extent, by induction of plant defenses without causing major alterations in plant metabolism. This study provides new insights into the modes of action of RLs on the wheat-Z. tritici pathosystem and highlights the potential interest in Rh-Est-C12, a low-fitness cost molecule, to control this pathogen.