RESUMO
The repertoire of modifications to bile acids and related steroidal lipids by host and microbial metabolism remains incompletely characterized. To address this knowledge gap, we created a reusable resource of tandem mass spectrometry (MS/MS) spectra by filtering 1.2 billion publicly available MS/MS spectra for bile-acid-selective ion patterns. Thousands of modifications are distributed throughout animal and human bodies as well as microbial cultures. We employed this MS/MS library to identify polyamine bile amidates, prevalent in carnivores. They are present in humans, and their levels alter with a diet change from a Mediterranean to a typical American diet. This work highlights the existence of many more bile acid modifications than previously recognized and the value of leveraging public large-scale untargeted metabolomics data to discover metabolites. The availability of a modification-centric bile acid MS/MS library will inform future studies investigating bile acid roles in health and disease.
Assuntos
Ácidos e Sais Biliares , Microbioma Gastrointestinal , Metabolômica , Espectrometria de Massas em Tandem , Animais , Humanos , Ácidos e Sais Biliares/química , Metabolômica/métodos , Poliaminas , Espectrometria de Massas em Tandem/métodos , Bases de Dados de Compostos QuímicosRESUMO
Staphylococcus aureus bacteremia (SaB) causes significant disease in humans, carrying mortality rates of â¼25%. The ability to rapidly predict SaB patient responses and guide personalized treatment regimens could reduce mortality. Here, we present a resource of SaB prognostic biomarkers. Integrating proteomic and metabolomic techniques enabled the identification of >10,000 features from >200 serum samples collected upon clinical presentation. We interrogated the complexity of serum using multiple computational strategies, which provided a comprehensive view of the early host response to infection. Our biomarkers exceed the predictive capabilities of those previously reported, particularly when used in combination. Last, we validated the biological contribution of mortality-associated pathways using a murine model of SaB. Our findings represent a starting point for the development of a prognostic test for identifying high-risk patients at a time early enough to trigger intensive monitoring and interventions.
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Bacteriemia/sangue , Bacteriemia/mortalidade , Infecções Estafilocócicas/sangue , Infecções Estafilocócicas/mortalidade , Staphylococcus aureus/patogenicidade , Animais , Bacteriemia/metabolismo , Biomarcadores/sangue , Biomarcadores/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Metabolômica/métodos , Camundongos , Pessoa de Meia-Idade , Prognóstico , Proteômica/métodos , Fatores de Risco , Infecções Estafilocócicas/metabolismoRESUMO
To gain insight into the stability of the microbial communities that inhabit our skin, Oh et al., in a tour-de-force effort, map the human skin metagenomes over time. Remarkably, their data indicate that the individual, not the environment, primarily drives the composition of skin microbial communities.
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Amigos , Metagenoma , Meio Ambiente , Humanos , PeleRESUMO
Determining the structure and phenotypic context of molecules detected in untargeted metabolomics experiments remains challenging. Here we present reverse metabolomics as a discovery strategy, whereby tandem mass spectrometry spectra acquired from newly synthesized compounds are searched for in public metabolomics datasets to uncover phenotypic associations. To demonstrate the concept, we broadly synthesized and explored multiple classes of metabolites in humans, including N-acyl amides, fatty acid esters of hydroxy fatty acids, bile acid esters and conjugated bile acids. Using repository-scale analysis1,2, we discovered that some conjugated bile acids are associated with inflammatory bowel disease (IBD). Validation using four distinct human IBD cohorts showed that cholic acids conjugated to Glu, Ile/Leu, Phe, Thr, Trp or Tyr are increased in Crohn's disease. Several of these compounds and related structures affected pathways associated with IBD, such as interferon-γ production in CD4+ T cells3 and agonism of the pregnane X receptor4. Culture of bacteria belonging to the Bifidobacterium, Clostridium and Enterococcus genera produced these bile amidates. Because searching repositories with tandem mass spectrometry spectra has only recently become possible, this reverse metabolomics approach can now be used as a general strategy to discover other molecules from human and animal ecosystems.
Assuntos
Amidas , Ácidos e Sais Biliares , Ésteres , Ácidos Graxos , Metabolômica , Animais , Humanos , Bifidobacterium/metabolismo , Ácidos e Sais Biliares/química , Ácidos e Sais Biliares/metabolismo , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Clostridium/metabolismo , Estudos de Coortes , Doença de Crohn/metabolismo , Enterococcus/metabolismo , Ésteres/química , Ésteres/metabolismo , Ácidos Graxos/química , Ácidos Graxos/metabolismo , Doenças Inflamatórias Intestinais/metabolismo , Metabolômica/métodos , Fenótipo , Receptor de Pregnano X/metabolismo , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem , Amidas/química , Amidas/metabolismoRESUMO
Bacteria in the gastrointestinal tract produce amino acid bile acid amidates that can affect host-mediated metabolic processes1-6; however, the bacterial gene(s) responsible for their production remain unknown. Herein, we report that bile salt hydrolase (BSH) possesses dual functions in bile acid metabolism. Specifically, we identified a previously unknown role for BSH as an amine N-acyltransferase that conjugates amines to bile acids, thus forming bacterial bile acid amidates (BBAAs). To characterize this amine N-acyltransferase BSH activity, we used pharmacological inhibition of BSH, heterologous expression of bsh and mutants in Escherichia coli and bsh knockout and complementation in Bacteroides fragilis to demonstrate that BSH generates BBAAs. We further show in a human infant cohort that BBAA production is positively correlated with the colonization of bsh-expressing bacteria. Lastly, we report that in cell culture models, BBAAs activate host ligand-activated transcription factors including the pregnane X receptor and the aryl hydrocarbon receptor. These findings enhance our understanding of how gut bacteria, through the promiscuous actions of BSH, have a significant role in regulating the bile acid metabolic network.
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Aciltransferases , Amidoidrolases , Aminas , Ácidos e Sais Biliares , Biocatálise , Microbioma Gastrointestinal , Humanos , Aciltransferases/metabolismo , Amidoidrolases/metabolismo , Aminas/química , Aminas/metabolismo , Bacteroides fragilis/enzimologia , Bacteroides fragilis/genética , Bacteroides fragilis/metabolismo , Ácidos e Sais Biliares/química , Ácidos e Sais Biliares/metabolismo , Estudos de Coortes , Escherichia coli/enzimologia , Escherichia coli/genética , Escherichia coli/metabolismo , Microbioma Gastrointestinal/fisiologia , Ligantes , Receptor de Pregnano X/metabolismo , Receptores de Hidrocarboneto Arílico/metabolismo , Fatores de Transcrição/metabolismo , Lactente , Técnicas de Cultura de CélulasRESUMO
Although eukaryotic nuclei contain distinct architectural structures associated with noncoding RNAs (ncRNAs), their potential relationship to regulated transcriptional programs remains poorly understood. Here, we report that methylation/demethylation of Polycomb 2 protein (Pc2) controls relocation of growth-control genes between Polycomb bodies (PcGs) and interchromatin granules (ICGs) in response to growth signals. This movement is the consequence of binding of methylated and unmethylated Pc2 to the ncRNAs TUG1 and MALAT1/NEAT2, located in PcGs and ICGs, respectively. These ncRNAs mediate assembly of multiple corepressors/coactivators and can serve to switch mark recognition by "readers" of the histone code. Additionally, binding of NEAT2 to unmethylated Pc2 promotes E2F1 SUMOylation, leading to activation of the growth-control gene program. These observations delineate a molecular pathway linking the actions of subnuclear structure-specific ncRNAs and nonhistone protein methylation to relocation of transcription units in the three-dimensional space of the nucleus, thus achieving coordinated gene expression programs.
Assuntos
Núcleo Celular/metabolismo , Regulação da Expressão Gênica , RNA não Traduzido/metabolismo , Proteínas Repressoras/metabolismo , Sequência de Aminoácidos , Linhagem Celular , Cromatina/metabolismo , Fator de Transcrição E2F1/metabolismo , Células HeLa , Humanos , Ligases , Metilação , Metiltransferases/metabolismo , Dados de Sequência Molecular , Proteínas do Grupo Polycomb , RNA Longo não Codificante , Proteínas Repressoras/química , Sumoilação , Transcrição Gênica , Ubiquitina-Proteína Ligases , UbiquitinaçãoRESUMO
Fungus-growing ants depend on a fungal mutualist that can fall prey to fungal pathogens. This mutualist is cultivated by these ants in structures called fungus gardens. Ants exhibit weeding behaviors that keep their fungus gardens healthy by physically removing compromised pieces. However, how ants detect diseases of their fungus gardens is unknown. Here, we applied the logic of Koch's postulates using environmental fungal community gene sequencing, fungal isolation, and laboratory infection experiments to establish that Trichoderma spp. can act as previously unrecognized pathogens of Trachymyrmex septentrionalis fungus gardens. Our environmental data showed that Trichoderma are the most abundant noncultivar fungi in wild T. septentrionalis fungus gardens. We further determined that metabolites produced by Trichoderma induce an ant weeding response that mirrors their response to live Trichoderma. Combining ant behavioral experiments with bioactivity-guided fractionation and statistical prioritization of metabolites in Trichoderma extracts demonstrated that T. septentrionalis ants weed in response to peptaibols, a specific class of secondary metabolites known to be produced by Trichoderma fungi. Similar assays conducted using purified peptaibols, including the two previously undescribed peptaibols trichokindins VIII and IX, suggested that weeding is likely induced by peptaibols as a class rather than by a single peptaibol metabolite. In addition to their presence in laboratory experiments, we detected peptaibols in wild fungus gardens. Our combination of environmental data and laboratory infection experiments strongly support that peptaibols act as chemical cues of Trichoderma pathogenesis in T. septentrionalis fungus gardens.
Assuntos
Formigas , Infecção Laboratorial , Trichoderma , Animais , Formigas/fisiologia , Jardins , Sinais (Psicologia) , Simbiose , PeptaibolsRESUMO
Metabolites exuded by primary producers comprise a significant fraction of marine dissolved organic matter, a poorly characterized, heterogenous mixture that dictates microbial metabolism and biogeochemical cycling. We present a foundational untargeted molecular analysis of exudates released by coral reef primary producers using liquid chromatography-tandem mass spectrometry to examine compounds produced by two coral species and three types of algae (macroalgae, turfing microalgae, and crustose coralline algae [CCA]) from Mo'orea, French Polynesia. Of 10,568 distinct ion features recovered from reef and mesocosm waters, 1,667 were exuded by producers; the majority (86%) were organism specific, reflecting a clear divide between coral and algal exometabolomes. These data allowed us to examine two tenets of coral reef ecology at the molecular level. First, stoichiometric analyses show a significantly reduced nominal carbon oxidation state of algal exometabolites than coral exometabolites, illustrating one ecological mechanism by which algal phase shifts engender fundamental changes in the biogeochemistry of reef biomes. Second, coral and algal exometabolomes were differentially enriched in organic macronutrients, revealing a mechanism for reef nutrient-recycling. Coral exometabolomes were enriched in diverse sources of nitrogen and phosphorus, including tyrosine derivatives, oleoyl-taurines, and acyl carnitines. Exometabolites of CCA and turf algae were significantly enriched in nitrogen with distinct signals from polyketide macrolactams and alkaloids, respectively. Macroalgal exometabolomes were dominated by nonnitrogenous compounds, including diverse prenol lipids and steroids. This study provides molecular-level insights into biogeochemical cycling on coral reefs and illustrates how changing benthic cover on reefs influences reef water chemistry with implications for microbial metabolism.
Assuntos
Antozoários/metabolismo , Matéria Orgânica Dissolvida/análise , Alga Marinha/metabolismo , Animais , Antozoários/genética , Antozoários/crescimento & desenvolvimento , Carbono/metabolismo , Recifes de Corais , Ecossistema , Biologia Marinha/métodos , Metabolômica/métodos , Nitrogênio/metabolismo , Nutrientes , Fósforo/metabolismo , Polinésia , Água do Mar/química , Alga Marinha/genética , Alga Marinha/crescimento & desenvolvimentoRESUMO
Metals are important cofactors in the metabolic processes of cyanobacteria, including photosynthesis, cellular respiration, DNA replication, and the biosynthesis of primary and secondary metabolites. In adaptation to the marine environment, cyanobacteria use metallophores to acquire trace metals when necessary as well as to reduce potential toxicity from excessive metal concentrations. Leptochelins A-C were identified as structurally novel metallophores from three geographically dispersed cyanobacteria of the genus Leptothoe. Determination of the complex structures of these metabolites presented numerous challenges, but they were ultimately solved using integrated data from NMR, mass spectrometry and deductions from the biosynthetic gene cluster. The leptochelins are comprised of halogenated linear NRPS-PKS hybrid products with multiple heterocycles that have potential for hexadentate and tetradentate coordination with metal ions. The genomes of the three leptochelin producers were sequenced, and retrobiosynthetic analysis revealed one candidate biosynthetic gene cluster (BGC) consistent with the structure of leptochelin. The putative BGC is highly homologous in all three Leptothoe strains, and all possess genetic signatures associated with metallophores. Postcolumn infusion of metals using an LC-MS metabolomics workflow performed with leptochelins A and B revealed promiscuous binding of iron, copper, cobalt, and zinc, with greatest preference for copper. Iron depletion and copper toxicity experiments support the hypothesis that leptochelin metallophores may play key ecological roles in iron acquisition and in copper detoxification. In addition, the leptochelins possess significant cytotoxicity against several cancer cell lines.
Assuntos
Cianobactérias , Cianobactérias/metabolismo , Cianobactérias/química , Cianobactérias/genética , Humanos , Família Multigênica , Linhagem Celular Tumoral , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/metabolismoRESUMO
The human gut microbiome has been linked to numerous digestive disorders, but its metabolic products have been much less well characterized, in part due to the expense of untargeted metabolomics and lack of ability to process the data. In this review, we focused on the rapidly expanding information about the bile acid repertoire produced by the gut microbiome, including the impacts of bile acids on a wide range of host physiological processes and diseases, and discussed the role of short-chain fatty acids and other important gut microbiome-derived metabolites. Of particular note is the action of gut microbiome-derived metabolites throughout the body, which impact processes ranging from obesity to aging to disorders traditionally thought of as diseases of the nervous system, but that are now recognized as being strongly influenced by the gut microbiome and the metabolites it produces. We also highlighted the emerging role for modifying the gut microbiome to improve health or to treat disease, including the "engineered native bacteria'' approach that takes bacterial strains from a patient, modifies them to alter metabolism, and reintroduces them. Taken together, study of the metabolites derived from the gut microbiome provided insights into a wide range of physiological and pathophysiological processes, and has substantial potential for new approaches to diagnostics and therapeutics of disease of, or involving, the gastrointestinal tract.
Assuntos
Microbioma Gastrointestinal , Microbiota , Humanos , Microbioma Gastrointestinal/fisiologia , Ácidos e Sais Biliares/metabolismo , Metaboloma , Microrganismos Geneticamente Modificados , Ácidos Graxos VoláteisRESUMO
Metabolites from feces provide important insights into the functionality of the gut microbiome. As immediate freezing is not always feasible in gut microbiome studies, there is a need for sampling protocols that provide the stability of the fecal metabolome and microbiome at room temperature (RT). Here, we investigated the stability of various metabolites and the microbiome (16S rRNA) in feces collected in 95% ethanol (EtOH) and commercially available sample collection kits with specific preservatives OMNImetâ¢GUT/OMNIgeneâ¢GUT. To simulate field-collection scenarios, the samples were stored at different temperatures at varying durations (24 h + 4 °C, 24 h RT, 36 h RT, 48 h RT, and 7 days RT) and compared to aliquots immediately frozen at -80 °C. We applied several targeted and untargeted metabolomics platforms to measure lipids, polar metabolites, endocannabinoids, short-chain fatty acids (SCFAs), and bile acids (BAs). We found that SCFAs in the nonstabilized samples increased over time, while a stable profile was recorded in sample aliquots stored in 95% EtOH and OMNImetâ¢GUT. When comparing the metabolite levels between aliquots stored at room temperature and at +4 °C, we detected several changes in microbial metabolites, including multiple BAs and SCFAs. Taken together, we found that storing samples at RT and stabilizing them in 95% EtOH yielded metabolomic results comparable to those from flash freezing. We also found that the overall composition of the microbiome did not vary significantly between different storage types. However, notable differences were observed in the α diversity. Altogether, the stability of the metabolome and microbiome in 95% EtOH provided results similar to those of the validated commercial collection kits OMNImetâ¢GUT and OMNIgeneâ¢GUT, respectively.
Assuntos
Etanol , Fezes , Microbioma Gastrointestinal , Metabolômica , Etanol/metabolismo , Etanol/análise , Fezes/microbiologia , Fezes/química , Humanos , Manejo de Espécimes/métodos , RNA Ribossômico 16S , TemperaturaRESUMO
MOTIVATION: Annotation of the mass signals is still the biggest bottleneck for the untargeted mass spectrometry analysis of complex mixtures. Molecular networks are being increasingly adopted by the mass spectrometry community as a tool to annotate large-scale experiments. We have previously shown that the process of propagating annotations from spectral library matches on molecular networks can be automated using Network Annotation Propagation (NAP). One of the limitations of NAP is that the information for the spectral matches is only propagated locally, to the first neighbor of a spectral match. Here, we show that annotation propagation can be expanded to nodes not directly connected to spectral matches using random walks on graphs, introducing the ChemWalker python library. RESULTS: Similarly to NAP, ChemWalker relies on combinatorial in silico fragmentation results, performed by MetFrag, searching biologically relevant databases. Departing from the combination of a spectral network and the structural similarity among candidate structures, we have used MetFusion Scoring function to create a weight function, producing a weighted graph. This graph was subsequently used by the random walk to calculate the probability of 'walking' through a set of candidates, departing from seed nodes (represented by spectral library matches). This approach allowed the information propagation to nodes not directly connected to the spectral library match. Compared with NAP, ChemWalker has a series of improvements, on running time, scalability and maintainability and is available as a standalone python package. AVAILABILITY AND IMPLEMENTATION: ChemWalker is freely available at https://github.com/computational-chemical-biology/ChemWalker. CONTACT: ridasilva@usp.br. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Assuntos
Bibliotecas , Bases de Dados Factuais , Biblioteca Gênica , Espectrometria de Massas , ProbabilidadeRESUMO
BACKGROUND: Human milk is unquestionably beneficial for preterm infants. We investigated how the transition from tube to oral/breastfeeding impacts the preterm infants' oral and gut microbiome and metabolome. METHODS: We analyzed stool, saliva, and milk samples collected from a cohort of preterm infants enrolled in the MAP Study, a prospective observational trial. The microbiome and metabolome of the samples were analyzed from 4 longitudinal sample time points, 2 during tube feeds only and 2 after the initiation of oral/breastfeeding. RESULTS: We enrolled 11 mother-infant dyads (gestational age = 27.9 (23.4-32.2)) and analyzed a total of 39 stool, 44 saliva, and 43 milk samples over 4 timepoints. In saliva samples, there was a shift towards increased Streptococcus and decreased Staphylococcus after oral feeding/breastfeeding initiation (p < 0.05). Milk sample metabolites were strongly influenced by the route of feeding and milk type (p < 0.05) and represented the pathways of Vitamin E metabolism, Vitamin B12 metabolism, and Tryptophan metabolism. CONCLUSION: Our analysis demonstrated that the milk and preterm infant's saliva microbiome and metabolome changed over the course of the first four to 5 months of life, coinciding with the initiation of oral/breastfeeds. IMPACT: The microbiome and metabolome is altered in the infant's saliva but not their stool, and in mother's milk when feeds are transitioned from tube to oral/breastfeeding. We assessed the relationship between the gut and oral microbiome/metabolome with the milk microbiome/metabolome over a longitudinal period of time in preterm babies. Metabolites that changed in the infants saliva after the initiation of oral feeds have the potential to be used as biomarkers for disease risk.
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In this Article, the sentence: "After 7 months of HFD, MUP-uPA mice developed HCC15, which contained numerous (usually 50-100 per tumour) non-recurrent coding mutations in pathways that are mutated in human HCC (Fig. 2d and Extended Data Fig. 6a).", should have read: "After 7 months of HFD, MUP-uPA mice developed HCC15, which contained numerous (usually 50-100 per tumour) non-recurrent mutations in pathways that are mutated in human HCC (Fig. 2d and Extended Data Fig. 6a).". This has been corrected online. In Extended Data Fig. 6a and b, which show the number of point mutations identified per sample and the mutational signatures, all sequence variants (including non-coding mutations) are shown. Fig. 2d also presents all variants compared to human mutations. In the Supplementary Information to this Amendment, we now provide the comparisons of all variants and coding variants to human mutations.
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The leaf homogenate of Psychotria insularum is widely used in Samoan traditional medicine to treat inflammation associated with fever, body aches, swellings, wounds, elephantiasis, incontinence, skin infections, vomiting, respiratory infections, and abdominal distress. However, the bioactive components and underlying mechanisms of action are unknown. We used chemical genomic analyses in the model organism Saccharomyces cerevisiae (baker's yeast) to identify and characterize an iron homeostasis mechanism of action in the traditional medicine as an unfractionated entity to emulate its traditional use. Bioactivity-guided fractionation of the homogenate identified two flavonol glycosides, rutin and nicotiflorin, each binding iron in an ion-dependent molecular networking metabolomics analysis. Translating results to mammalian immune cells and traditional application, the iron chelator activity of the P. insularum homogenate or rutin decreased proinflammatory and enhanced anti-inflammatory cytokine responses in immune cells. Together, the synergistic power of combining traditional knowledge with chemical genomics, metabolomics, and bioassay-guided fractionation provided molecular insight into a relatively understudied Samoan traditional medicine and developed methodology to advance ethnobotany.
Assuntos
Anti-Inflamatórios/análise , Flavonoides/isolamento & purificação , Quelantes de Ferro/análise , Fenóis/isolamento & purificação , Psychotria/química , Rutina/isolamento & purificação , Animais , Avaliação Pré-Clínica de Medicamentos , Etnobotânica , Feminino , Genômica , Masculino , Medicina Tradicional , Metabolômica , Camundongos Endogâmicos C57BL , Plantas Medicinais/química , Saccharomyces cerevisiae , SamoaRESUMO
spectrum_utils is a Python package for mass spectrometry data processing and visualization. Since its introduction, spectrum_utils has grown into a fundamental software solution that powers various applications in proteomics and metabolomics, ranging from spectrum preprocessing prior to spectrum identification and machine learning applications to spectrum plotting from online data repositories and assisting data analysis tasks for dozens of other projects. Here, we present updates to spectrum_utils, which include new functionality to integrate mass spectrometry community data standards, enhanced mass spectral data processing, and unified mass spectral data visualization in Python. spectrum_utils is freely available as open source at https://github.com/bittremieux/spectrum_utils.
Assuntos
Proteômica , Software , Espectrometria de Massas , Proteômica/métodos , Metabolômica , Aprendizado de MáquinaRESUMO
Bile acids play key roles in nutrient uptake, inflammation, signaling, and microbiome composition. While previous bile acid analyses have primarily focused on profiling 5 canonical primary and secondary bile acids and their glycine and taurine amino acid-bile acid (AA-BA) conjugates, recent studies suggest that many other microbial conjugated bile acids (or MCBAs) exist. MCBAs are produced by the gut microbiota and serve as biomarkers, providing information about early disease onset and gut health. Here we analyzed 8 core bile acids synthetically conjugated with 22 proteinogenic and nonproteogenic amino acids totaling 176 MCBAs. Since many of the conjugates were isomeric and only 42 different m/z values resulted from the 176 MCBAs, a platform coupling liquid chromatography, ion mobility spectrometry, and mass spectrometry (LC-IMS-MS) was used for their separation. Their molecular characteristics were then used to create an in-house extended bile acid library for a combined total of 182 unique compounds. Additionally, â¼250 rare bile acid extracts were also assessed to provide additional resources for bile acid profiling and identification. This library was then applied to healthy mice dosed with antibiotics and humans having fecal microbiota transplantation (FMT) to assess the MCBA presence and changes in the gut before and after each perturbation.
Assuntos
Aminoácidos , Ácidos e Sais Biliares , Humanos , Camundongos , Animais , Isomerismo , Espectrometria de Massas , EsteroidesRESUMO
We present ReDU ( https://redu.ucsd.edu/ ), a system for metadata capture of public mass spectrometry-based metabolomics data, with validated controlled vocabularies. Systematic capture of knowledge enables the reanalysis of public data and/or co-analysis of one's own data. ReDU enables multiple types of analyses, including finding chemicals and associated metadata, comparing the shared and different chemicals between groups of samples, and metadata-filtered, repository-scale molecular networking.
Assuntos
Bases de Dados de Compostos Químicos , Espectrometria de Massas , Metabolômica/métodos , Software , Metadados , Modelos QuímicosRESUMO
Untargeted mass spectrometry is employed to detect small molecules in complex biospecimens, generating data that are difficult to interpret. We developed Qemistree, a data exploration strategy based on the hierarchical organization of molecular fingerprints predicted from fragmentation spectra. Qemistree allows mass spectrometry data to be represented in the context of sample metadata and chemical ontologies. By expressing molecular relationships as a tree, we can apply ecological tools that are designed to analyze and visualize the relatedness of DNA sequences to metabolomics data. Here we demonstrate the use of tree-guided data exploration tools to compare metabolomics samples across different experimental conditions such as chromatographic shifts. Additionally, we leverage a tree representation to visualize chemical diversity in a heterogeneous collection of samples. The Qemistree software pipeline is freely available to the microbiome and metabolomics communities in the form of a QIIME2 plugin, and a global natural products social molecular networking workflow.
Assuntos
Espectrometria de Massas/métodos , Metabolômica , Algoritmos , Análise por Conglomerados , DNA/química , Impressões Digitais de DNA , Bases de Dados Factuais , Ecologia , Análise de Alimentos , Microbiota , Análise Multivariada , Software , Espectrometria de Massas em Tandem , Fluxo de TrabalhoRESUMO
Schizophrenia is a devastating psychiatric illness that detrimentally affects a significant portion of the worldwide population. Aging of schizophrenia patients is associated with reduced longevity, but the potential biological factors associated with aging in this population have not yet been investigated in a global manner. To address this gap in knowledge, the present study assesses proteomics and metabolomics profiles in the plasma of subjects afflicted with schizophrenia compared to non-psychiatric control patients over six decades of life. Global, unbiased analyses of circulating blood plasma can provide knowledge of prominently dysregulated molecular pathways and their association with schizophrenia, as well as features of aging and gender in this disease. The resulting data compiled in this study represent a compendium of molecular changes associated with schizophrenia over the human lifetime. Supporting the clinical finding of schizophrenia's association with more rapid aging, both schizophrenia diagnosis and age significantly influenced the plasma proteome in subjects assayed. Schizophrenia was broadly associated with prominent dysregulation of inflammatory and metabolic system components. Proteome changes demonstrated increased abundance of biomarkers for risk of physiologic comorbidities of schizophrenia, especially in younger individuals. These findings advance our understanding of the molecular etiology of schizophrenia and its associated comorbidities throughout the aging process.