LuYuxing/MetaBench huggingface dataset:
Question: Write a study description for the study titled 'Unveiling superior phenol detoxification and degradation ability in Candida tropicalis SHC-03: A comparative study with Saccharomyces cerevisiae BY4742'.
Answer: This study examined the phenol degradation capabilities and oxidative stress responses of Candida tropicalis SHC-03, demonstrating its metabolic superiority and resilience compared to Saccharomyces cerevisiae BY4742 in a culture medium with phenol as the sole carbon source. Through comparative growth, transcriptomic and metabolomic analyses under different phenol concentrations, this study revealed C. tropicalis SHC-03's specialized adaptations for thriving in phenol as the sole carbon source environments. These include a strategic shift from carbohydrate metabolism to enhanced phenol degradation pathways, highlighted by the significant upregulation of genes for Phenol 2-monoxygenase and Catechol 1,2-dioxygenase. Despite phenol levels reaching 1.8 g/L, C. tropicalis exhibits a robust oxidative stress response, efficiently managing ROS through antioxidative pathways and the upregulation of genes for peroxisomal proteins like PEX2, PEX13 and PMP34. Concurrently, there was significant upregulation of genes associated with membrane components and transmembrane transporters, enhancing the cell's capacity for substance exchange and signal transduction. Especially, when the phenol concentration was 1.6 g/L and 1.8 g/L, the degradation rates of C. tropicalis towards it were 99.47% and 95.91%, respectively. Conversely, S. cerevisiae BY4742 shows limited metabolic response, with pronounced growth inhibition and lack of phenol degradation. Therefore, our study not only sheds light on the molecular mechanisms underpinning phenol tolerance and degradation in C. tropicalis but also positions this yeast as a promising candidate for environmental and industrial processes aimed at mitigating phenol pollution.
Question: Write a study description for the study titled 'Prevotella copri mediated caffeine metabolism involves ferroptosis of osteoblasts in osteoarthritis'.
Answer: There is positive causality between coffee consumption and osteoarthritis (OA), however, whether gut microbiota is involved in it needs to be discussed. Here, we observed that, in caffeine consumers, fecal Prevotella copri (P. copri) abundance was positively correlated with subchondral bone mass, serum caffeine concentration was negatively correlated with bone mass, and fecal P. copri was negatively correlated with serum caffeine. In OA model, caffeine intake aggravated articular cartilage destruction, bone mass loss and intestinal barrier damage, on the contrary, paraxanthine intake, reversed the above lesions. Importantly, after intestinal P. copri supplement, caffeine induced lesions in OA mice was effectively alleviated. Mechanically, P. copri has the potential to metabolize caffeine into paraxanthine, and this effect could alleviate the ferroptosis of osteoblast in OA model. This study screened out that P. copri, an endogenous bacteria, has the ability to metabolize caffeine and revealed the effects of it on OA progression.
Question: Write a study description for the study titled 'Defective mitochondrial COX1 translation due to loss of COX14 function triggers ROS-induced inflammation in liver'.
Answer: Mitochondrial oxidative phosphorylation (OXPHOS) fuels cellular ATP demands. OXPHOS defects lead to severe human disorders with unexplained tissue specific pathologies. Mitochondrial gene expression is essential for OXPHOS biogenesis since core subunits of the complexes are mitochondrial-encoded. COX14 is required for translation of COX1, the central mitochondrial-encoded subunit of complex IV. Here we generated a COX14 mutant mouse corresponding to a patient with complex IV deficiency. COX14M19I mice display broad tissue-specific pathologies. A hallmark phenotype is severe liver inflammation linked to release of mitochondrial RNA into the cytosol sensed by RIG-1 pathway. We find that mitochondrial RNA release is triggered by increased reactive oxygen species production in the deficiency of complex IV. Additionally, we generated a COA3Y72C mouse, affected in an assembly factor in early COX1 biogenesis, which displayed a similar yet milder inflammatory phenotype. Our study provides mechanistic insight into how defective mitochondrial gene expression causes tissue-specific inflammation.
Question: Write a study description for the study titled 'Creating a Reliable Mass Spectral–Retention Time Library for All Ion Fragmentation-Based Metabolomics'.
Answer: Accurate metabolite identification remains one of the primary challenges in a metabolomics study. A reliable chemical spectral library increases the confidence in annotation, and the availability of raw and annotated data in public databases facilitates the transfer of Liquid chromatography coupled to mass spectrometry (LC–MS) methods across laboratories. Here, we illustrate how the combination of MS2 spectra, accurate mass, and retention time can improve the confidence of annotation and provide techniques to create a reliable library for all ion fragmentation (AIF) data with a focus on the characterization of the retention time. The resulting spectral library incorporates information on adducts and in-source fragmentation in AIF data, while noise peaks are effectively minimized through multiple deconvolution processes. We also report the development of the Mass Spectral LIbrary MAnager (MS-LIMA) tool to accelerate library sharing and transfer across laboratories. This library construction strategy improves the confidence in annotation for AIF data in LC–MS-based metabolomics and will facilitate the sharing of retention time and mass spectral data in the metabolomics community.
Question: Write a study description for the study titled 'Molecular changes in cancer cells exposed to an HDAC inhibitor: A metabolomics approach'.
Answer: Histone deacetylase (HDAC) inhibitors are part of a new generation of epigenetic drugs for cancer treatment. It is known that histone acetylation plays a key role in controlling essential chromosome functions, including gene regulation, and this process has been linked with cancer development and progression. Better understanding of molecular mechanisms involving HDAC inhibitors is needed for the design of new targeted drugs, and also to evaluate the effectiveness of current treatments. In this study, an untargeted metabolomics approach was used to identify intracellular metabolite deregulation after treating cancer cell lines with the HDAC inhibitor HC-Toxin. Metabolomics analysis was performed using high resolution mass spectrometry, in combination with univariate and multivariate statistics and pathway analysis. HDAC inhibition showed highly specific metabolic changes in cancer cell lines compared to non-cancerous cells. In particular, N-acetyl-L-cysteine, N-acetylmethionine, and N-acetyl-L-carnitine showed a dose dependent change. Moreover, pathways controlling protein biosynthesis, as well as tryptophan, cysteine and methionine metabolism were significantly altered by HDAC inhibition. This study illustrates that HDAC inhibition has multiple effects on different metabolic pathways and our results can be extrapolated to inform on the molecular transitions in human cells.
Question: Write a study description for the study titled '"Tissue- and Pathway-Specific Metabolomic Profiles of the Steroid Receptor Coactivator (SRC) family"'.
Answer: "The rapidly growing family of coregulators of nuclear receptors includes coactivators that promote transcription and corepressors that harbor the opposing function. In recent years, coregulators have begun to emerge as important regulators of metabolic homeostasis, including the p160 Steroid Receptor Coactivator (SRC) family. Members of the SRC family have been ascribed important roles in control of gluconeogenesis in liver and fatty acid oxidation in skeletal muscle. To provide a deeper and more granular understanding of the metabolic impact of SRC family members, we have performed targeted metabolomics analysis of key metabolic byproducts of glucose, fatty acid, and amino acid metabolism in mice with global knockout of SRC-1, SRC-2, or SRC-3. We measured amino acids, acyl carnitines, and organic acids in five tissues with key metabolic functions (liver, heart, skeletal muscle, brain, plasma) isolated from SRC-1, -2, or -3 knockout mice and their wild-type littermates in the fed and fasted conditions, thereby unveiling unique metabolic functions of each SRC coactivator. Overall, we observed entire groups or subgroups of metabolites belonging to discrete metabolic pathways that were influenced in different tissues and/or feeding states due to ablation of individual SRC isoforms. Surprisingly, we identified very few metabolites that changed universally across the three SRC knockout models. These findings demonstrate that coactivator function has very limited redundancy even within the homologous SRC coactivator family. Furthermore, this work also demonstrates the use of metabolomics as a means for identifying novel metabolic regulatory functions of transcriptional coregulators."
Question: Write a study description for the study titled 'TFAM loss induces nuclear actin assembly upon mDia2 malonylation to promote liver cancer metastasis'.
Answer: The mechanisms underlying cancer metastasis remain poorly understood. Here, we report that TFAM deficiency rapidly and stably induced spontaneous lung metastasis in mice with liver cancer. Interestingly, unexpected polymerization of nuclear actin was observed in TFAM-knockdown HCC cells when cytoskeleton was examined. Polymerization of nuclear actin is causally linked to the high-metastatic ability of HCC cells by modulating chromatin accessibility and coordinating the expression of genes associated with extracellular matrix remodeling, angiogenesis, and cell migration. Mechanistically, TFAM deficiency blocked the TCA cycle and increased the intracellular malonyl-CoA levels. Malonylation of mDia2, which drives actin assembly, promotes its nuclear translocation. Importantly, inhibition of malonyl-CoA production or nuclear actin polymerization significantly impeded the spread of HCC cells in mice. Moreover, TFAM was significantly downregulated in metastatic HCC tissues and was associated with overall survival and time to tumor recurrence of HCC patients. Taken together, our study connects mitochondria to the metastasis of human cancer via uncovered mitochondria-to-nucleus retrograde signaling, indicating that TFAM may serve as an effective target to block HCC metastasis.
Question: Write a study description for the study titled 'ELAPOR1 induces the classical/progenitor subtype and contributes to reduced disease aggressiveness through metabolic reprogramming in pancreatic cancer'.
Answer: Pancreatic ductal adenocarcinoma (PDAC) is a heterogeneous disease with distinct molecular subtypes described as classical/progenitor and basal-like/squamous PDAC. We hypothesized that integrative transcriptome and metabolome approaches can identify candidate genes whose inactivation contributes to the development of the aggressive basal-like/squamous subtype. Using our integrated approach, we identified endosome-lysosome associated apoptosis and autophagy regulator 1 (ELAPOR1/KIAA1324) as a candidate tumor suppressor in both our NCI-UMD-German cohort and additional validation cohorts. Diminished ELAPOR1 expression was linked to high histological grade, advanced disease stage, the basal-like/squamous subtype, and reduced patient survival in PDAC. In vitro experiments demonstrated that ELAPOR1 transgene expression not only inhibited the migration and invasion of PDAC cells but also induced gene expression characteristics associated with the classical/progenitor subtype. Metabolome analysis of patient tumors and PDAC cells revealed a metabolic program associated with both upregulated ELAPOR1 and the classical/progenitor subtype, encompassing upregulated lipogenesis and downregulated amino acid metabolism. 1-Methylnicotinamide, a known oncometabolite derived from S-adenosylmethionine, was inversely associated with ELAPOR1 expression and promoted migration and invasion of PDAC cells in vitro. Taken together, our data suggest that enhanced ELAPOR1 expression promotes transcriptome and metabolome characteristics that are indicative of the classical/progenitor subtype, whereas its reduction associates with basal-like/squamous tumors with increased disease aggressiveness in PDAC patients. These findings position ELAPOR1 as a promising candidate for diagnostic and therapeutic targeting in PDAC.
Question: Write a study description for the study titled 'ms-mint: Targeted metabolomics with Python'.
Answer: Metabolomics has emerged as a mainstream approach for investigating the complex metabolic underpinnings of living systems. Over recent years, metabolomics has increasingly been applied to large cohort studies that tax the limits of existing computational tools. Though effective when applied to small datasets, many existing metabolomics software tools have three common shortcomings that limit their utility when applied to large studies: they store entire datasets in memory, they use batch-dependent fitting algorithms, and they use ambiguous representation of regions of interests leading to inconsistent peak-picking results across samples. To address this, we developed the mass-spectrometry metabolomics integrator (ms-mint), a Python library for processing, analyzing, and visualizing large LC-MS datasets. To enable reproducible large scale data processing tasks, ms-mint uses a region of interest (ROI)-based approach to extract data. We illustrate the function of this new tool using a large dataset (3,334 files) of standards and Staphylococcus aureus metabolite extracts. Via regression analyses, we show that ms-mint faithfully reproduces data generated from other software tools (R2 > 0.9999). Moreover, once ms-mint processing parameters have been set, analyses are fully automated and efficient (3334 files in less than 10 minutes) while maintaining a minimal memory footprint (~200MB). We demonstrate how the extendable open-source library can be used to efficiently process very large datasets using a deterministic and batch-independent protocol enabling targeted metabolomics at scale.
Question: Write a study description for the study titled 'Gut microbiota-driven regulation of queen bee ovarian metabolism'.
Answer: With the global prevalence of Varroa mites, more and more beekeepers resort to confining the queen bee in a queen cage to control mite infestation or to breed superior and robust queen bees. However, the impact of such practices on the queen bee remains largely unknown. Therefore, we subjected the queen bees to a 21-d egg-laying restriction treatment (from the egg stage to the emergence of adult worker bees) and analyzed the queen bees' ovarian metabolites and gut microbiota after 21 d, aiming to assess the queen bee's quality and assist beekeepers in better hive management. Our findings revealed a significant reduction in the relative expression levels of Vg and Hex110 genes in the ovaries of egg-laying-restricted queen bees compared to unrestricted egg-laying queens. The diversity of gut microbiota in the queen bee exhibited a notable decrease, accompanied by corresponding changes in the core bacterial species of the microbial community. Following egg-laying restriction, the activity of the queen bee's ovaries decreased, while the metabolism of glycerophospholipids remained or stored more lipid molecules, awaiting environmental changes for the queen bee to resume egg-laying promptly. Furthermore, we observed that Bombella in the queen bee's gut may regulate the queen's ovarian metabolism through tryptophan metabolism. These findings provide novel insights into the interplay among queen egg-laying, gut microbiota, and ovarian metabolism.
Question: Write a study description for the study titled 'Global ocean lipidomes show a universal relationship between temperature and lipid unsaturation'.
Answer: Global-scale surveys of plankton communities using “omics” techniques have revolutionized our understanding of the ocean. Lipidomics has demonstrated the potential to add further essential insights on ocean ecosystem function but has yet to be applied on a global scale. We analyzed 930 lipid samples across the global ocean using a uniform high-resolution accurate-mass mass spectrometry analytical workflow, revealing previously unknown characteristics of ocean planktonic lipidomes. Focusing on 10 molecularly diverse glycerolipid classes, we identified 1151 distinct lipid species, finding that fatty acid unsaturation (i.e., number of carbon-carbon double bonds) is fundamentally constrained by temperature. We predict substantial declines in the essential fatty acid eicosapentaenoic acid over the next century, which are likely to have serious deleterious effects on economically critical fisheries.
Question: Write a study description for the study titled 'SPE-IMS-MS: An automated platform for sub-sixty second surveillance of endogenous metabolites and xenobiotics in biofluids'.
Answer: Characterization of endogenous metabolites and xenobiotics is essential to deconvoluting the genetic and environmental causes of disease. However, surveillance of chemical exposure and disease-related changes in large cohorts requires an analytical platform that offers rapid measurement, high sensitivity, efficient separation, broad dynamic range, and application to an expansive chemical space. Here, we present a novel platform for small molecule analyses that addresses these requirements by combining solidphase extraction with ion mobility spectrometry and mass spectrometry (SPE-IMS-MS). This platform is capable of performing both targeted and global measurements of endogenous metabolites and xenobiotics in human biofluids with high reproducibility (CV <= 3%), sensitivity (LODs in the pM range in biofluids) and throughput (10-s sample-to-sample duty cycle). We report application of this platform to the analysis of human urine from patients with and without type 1 diabetes, where we observed statistically significant variations in the concentration of disaccharides and previously unreported chemical isomers. This SPE-IMS-MS platform overcomes many of the current challenges of large-scale metabolomic and exposomic analyses and offers a viable option for population and patient cohort screening in an effort to gain insights into disease processes and human environmental chemical exposure.
Question: Write a study description for the study titled 'L-serine enables reducing the virulence of Acinetobacter baumannii and modulating the SIRT1 pathway to eliminate the pathogen'.
Answer: The emergence of high-virulent Acinetobacter baumannii strains increases the mortality of patients and seriously affects their prognosis, which motivates us to explore novel ways to control such infections. In this study, gas chromatography-mass spectrometry was adopted to explore the metabolic difference between high- and low-virulent A. baumannii strains, and the decreased L-serine levels were identified as the most crucial biomarker in low-virulent A. baumannii strains. In vitro, L-serine reduced the virulence of A. baumannii to Beas 2B cells and inhibited the activation of NLRP3 inflammasome via decreasing the generation of ROS and mtROS and the release of inflammatory cytokines (IL-18 and IL-1β) through upregulating SIRT1. In vivo, the Galleria mellonella model was adopted. L-serine downregulated the levels of virulence genes (ompA, carO and omp33-36), reduced the mortality of A. baumannii to G. mellonella, and decreased the blacking speed as well as the degree of G. mellonella after infection. Taken together, we found that L-serine can reduce the virulence of A. baumannii and enhance the host’s defense against the pathogen, providing a novel strategy for the treatment of infections caused by A. baumannii.
Question: Write a study description for the study titled 'Metabolic reaction network-based recursive metabolite annotation for untargeted metabolomics (Aging fruit fly 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 'Targeted metabolomics analysis by LC-MS/MS for BMDCs infected with VSV'.
Answer: Virus-infected cells often exhibit dramatic cellular changes accompanied by altered mitochondrial function. The contribution of factors shaping the inner mitochondrial membrane (IMM) and cristae architecture on viral replication is insufficiently understood. Single cell transcriptomics applying vesicular stomatitis virus (VSV) infection suggests involvement of factors determining IMM architecture following infection. Consistently, inhibition of the F1Fo ATP synthase reduces viral replication which is associated with oligomerization of the complex and altered IMM structure. Moreover, deletion of mitochondrial contact site and cristae organizing system (MICOS) complex by targeting MIC60 results in reduced viral replication. Generation of Mic60inv/inv CD11c-Cre+ mice uncovers reduced crista junctions and viral replication in bone marrow-derived dendritic cells. Consequently, reduced viral replication in CD11c-expressing cells limits prolonged immune activation. Altogether, by linking the F1Fo ATP synthase and the MICOS complex to viral replication and immune activation, we describe links between the mitochondrial structure-metabolism and the immune response against viral infection.