50 research outputs found
Metabolomic database annotations query of elemental compositions: Mass accuracy is insufficient even at less than 1 ppm-0
<p><b>Copyright information:</b></p><p>Taken from "Metabolomic database annotations query of elemental compositions: Mass accuracy is insufficient even at less than 1 ppm"</p><p>BMC Bioinformatics 2006;7():234-234.</p><p>Published online 28 Apr 2006</p><p>PMCID:PMC1464138.</p><p>Copyright © 2006 Kind and Fiehn; licensee BioMed Central Ltd.</p
Metabolomic database annotations query of elemental compositions: Mass accuracy is insufficient even at less than 1 ppm-3
<p><b>Copyright information:</b></p><p>Taken from "Metabolomic database annotations query of elemental compositions: Mass accuracy is insufficient even at less than 1 ppm"</p><p>BMC Bioinformatics 2006;7():234-234.</p><p>Published online 28 Apr 2006</p><p>PMCID:PMC1464138.</p><p>Copyright © 2006 Kind and Fiehn; licensee BioMed Central Ltd.</p> formulae
Using Accurate Mass Gas ChromatographyâMass Spectrometry with the MINE Database for Epimetabolite Annotation
Mass spectrometry-based
untargeted metabolomics often detects statistically
significant metabolites that cannot be readily identified. Without
defined chemical structure, interpretation of the biochemical relevance
is not feasible. Epimetabolites are produced from canonical metabolites
by defined enzymatic reactions and may represent a large fraction
of the structurally unidentified metabolome. We here present a systematic
workflow for annotating unknown epimetabolites using high resolution
gas chromatographyâaccurate mass spectrometry with multiple
ionization techniques and stable isotope labeled derivatization methods.
We first determine elemental formulas, which are then used to query
the âmetabolic in-silico expansionâ database (MINE DB)
to obtain possible molecular structures that are predicted by enzyme
promiscuity from canonical pathways. Accurate mass fragmentation rules
are combined with in silico spectra prediction programs CFM-ID and
MS-FINDER to derive the best candidates. We validated the workflow
by correctly identifying 10 methylated nucleosides and 6 methylated
amino acids. We then employed this strategy to annotate eight unknown
compounds from cancer studies and other biological systems
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MS2Analyzer: A Software for Small Molecule Substructure Annotations from Accurate Tandem Mass Spectra
Systematic
analysis and interpretation of the large number of tandem
mass spectra (MS/MS) obtained in metabolomics experiments is a bottleneck
in discovery-driven research. MS/MS mass spectral libraries are small
compared to all known small molecule structures and are often not
freely available. MS2Analyzer was therefore developed to enable user-defined
searches of thousands of spectra for mass spectral features such as
neutral losses, <i>m</i>/<i>z</i> differences,
and product and precursor ions from MS/MS spectra in MSP/MGF files.
The software is freely available at http://fiehnlab.ucdavis.edu/projects/MS2Analyzer/. As the reference query set, 147 literature-reported neutral losses
and their corresponding substructures were collected. This set was
tested for accuracy of linking neutral loss analysis to substructure
annotations using 19â329 accurate mass tandem mass spectra
of structurally known compounds from the NIST11 MS/MS library. Validation
studies showed that 92.1 ± 6.4% of 13 typical neutral losses
such as acetylations, cysteine conjugates, or glycosylations are correct
annotating the associated substructures, while the absence of mass
spectra features does not necessarily imply the absence of such substructures.
Use of this tool has been successfully demonstrated for complex lipids
in microalgae
How Well Can We Predict Mass Spectra from Structures? Benchmarking Competitive Fragmentation Modeling for Metabolite Identification on Untrained Tandem Mass Spectra
Competitive Fragmentation Modeling for Metabolite Identification
(CFM-ID) is a machine learning tool to predict in silico tandem mass
spectra (MS/MS) for known or suspected metabolites for which chemical
reference standards are not available. As a machine learning tool,
it relies on both an underlying statistical model and an explicit
training set that encompasses experimental mass spectra for specific
compounds. Such mass spectra depend on specific parameters such as
collision energies, instrument types, and adducts which are accumulated
in libraries. Yet, ultimately prediction tools that are meant to cover
wide expanses of entities must be validated on cases that were not
included in the initial training and testing sets. Hence, we here
benchmarked the performance of CFM-ID 4.0 to correctly predict MS/MS
spectra for spectra that were not included in the CFM-ID training
set and for different mass spectrometry conditions. We used 609,456
experimental tandem spectra from the NIST20 mass spectral library
that were newly added to the previous NIST17 library version. We found
that CFM-IDâs highest energy prediction output would maximize
the capacity for library generation. Matching the experimental collision
energy with CFM-IDâs prediction energy produced the best results,
even for HCD-Orbitrap instruments. For benzenoids, better MS/MS predictions
were achieved than for heterocyclic compounds. However, when exploring
CFM-IDâs performance on 8,305 compounds at 40 eV HCD-Orbitrap
collision energy, >90% of the 20/80 split test compounds showed
<700
MS/MS similarity score. Instead of a stand-alone tool, CFM-ID 4.0
might be useful to boost candidate structures in the greater context
of identification workflows
Ultrafast Polyphenol Metabolomics of Red Wines Using MicroLC-MS/MS
The taste and quality of red wine
are determined by its highly
complex mixture of polyphenols and many other metabolites. No single
method can fully cover the full metabolome, but even for polyphenols
and related compounds, current methods proved inadequate. We optimized
liquid chromatography resolution and sensitivity using 1 mm i.d. columns
with microLC pumps and compared data-dependent to data-independent
(SWATH) MS/MS acquisitions. A high-throughput microLC-MS method was
developed with a 4 min gradient at 0.05 mL/min flow rate on a Kinetex
C18 column and Sciex TripleTOF mass spectrometry. Using the novel
software MS-DIAL, we structurally annotated 264 compounds including
165 polyphenols in six commercial red wines by accurate mass MS/MS
matching. As proof of concept, multivariate statistics revealed the
difference in the metabolite profiles of the six red wines, and regression
analysis linked the polyphenol contents to the taste of the red wines
Weighting Low-Intensity MS/MS Ions and <i>m</i>/<i>z</i> Frequency for Spectral Library Annotation
Calculating
spectral similarity is a fundamental step in MS/MS
data analysis in untargeted metabolomics experiments, as it facilitates
the identification of related spectra and the annotation of compounds.
To improve matching accuracy when querying an experimental mass spectrum
against a spectral library, previous approaches have proposed increasing
peak intensities for high m/z ranges.
These high m/z values tend to be
smaller in magnitude, yet they offer more crucial information for
identifying the chemical structure. Here, we evaluate the impact of
using these weights for identifying structurally related compounds
and mass spectral library searches. Additionally, we propose a weighting
approach that (i) takes into account the frequency of the m/z values within a spectral library in
order to assign higher importance to the most common peaks and (ii)
increases the intensity of lower peaks, similar to previous approaches.
To demonstrate our approach, we applied weighting preprocessing to
modified cosine, entropy, and fidelity distance metrics and benchmarked
it against previously reported weights. Our results demonstrate how
weighting-based preprocessing can assist in annotating the structure
of unknown spectra as well as identifying structurally similar compounds.
Finally, we examined scenarios in which the utilization of weights
resulted in diminished performance, pinpointing spectral features
where the application of weights might be detrimental
Beyond the Ground State: Predicting Electron Ionization Mass Spectra Using Excited-State Molecular Dynamics
Here, we provide an algorithm that introduces excited
states into
the molecular dynamics prediction of the 70 eV electron ionization
mass spectra. To decide the contributions of different electronic
states, the ionization cross section associated with relevant molecular
orbitals was calculated by the binaryâencounterâBethe
(BEB) model. We used a fast orthogonalization model/single and double
state configuration interaction (OM2/CISD) method to implement excited
states calculations and combined this with the GFN1-xTB semiempirical
model. Demonstrated by predicting the mass spectrum of urocanic acid,
we showed better accuracies to experimental spectra using excited-state
molecular dynamics than calculations that only used the ground-state
occupation. For several histidine pathway intermediates, we found
that excited-state corrections yielded an average of 73% more true
positive ions compared to the OM2 method when matching to experimental
spectra and 16% more true positive ions compared to the GFN method.
Importantly, the exited state models also correctly predict several
fragmentation reactions that were missing from both ground-state methods.
Overall, for 48 calculated molecules, we found the best average mass
spectral similarity scores for the mixed excited-state method compared
to the ground-state methods using either cosine, weighted dot score,
or entropy similarity calculations. Therefore, we recommend adding
excited-state calculations for predicting the electron ionization
mass spectra of small molecules in metabolomics
Environmental Tobacco Smoke Alters Metabolic Systems in Adult Rats
Human
exposure to environmental tobacco smoke (ETS) is associated
with an increased incidence of pulmonary and cardiovascular disease
and possibly lung cancer. Metabolomics can reveal changes in metabolic
networks in organisms under different physio-pathological conditions.
Our objective was to identify spatial and temporal metabolic alterations
with acute and repeated subchronic ETS exposure to understand mechanisms
by which ETS exposure may cause adverse physiological and structural
changes in the pulmonary and cardiovascular systems. Established and
validated metabolomics assays of the lungs, hearts. and blood of young
adult male rats following 1, 3, 8, and 21 days of exposure to ETS
along with day-matched sham control rats (<i>n</i> = 8)
were performed using gas chromatography time-of-flight mass spectrometry,
BinBase database processing, multivariate statistical modeling, and
MetaMapp biochemical mapping. A total of 489 metabolites were measured
in the lung, heart, and blood, of which 142 metabolites were identified
using a standardized metabolite annotation pipeline. Acute and repeated
subchronic exposure to ETS was associated with significant metabolic
changes in the lung related to energy metabolism, defense against
reactive oxygen species, substrate uptake and transport, nucleotide
metabolism, and substrates for structural components of collagen and
membrane lipids. Metabolic changes were least prevalent in heart tissues
but abundant in blood under repeated subchronic ETS exposure. Our
analyses revealed that ETS causes alterations in metabolic networks,
especially those associated with lung structure and function and found
as systemic signals in the blood. The metabolic changes suggest that
ETS exposure may adversely affects the mitochondrial respiratory chain,
lung elasticity, membrane integrity, redox states, cell cycle, and
normal metabolic and physiological functions of the lungs, even after
subchronic ETS exposure
Environmental Tobacco Smoke Alters Metabolic Systems in Adult Rats
Human
exposure to environmental tobacco smoke (ETS) is associated
with an increased incidence of pulmonary and cardiovascular disease
and possibly lung cancer. Metabolomics can reveal changes in metabolic
networks in organisms under different physio-pathological conditions.
Our objective was to identify spatial and temporal metabolic alterations
with acute and repeated subchronic ETS exposure to understand mechanisms
by which ETS exposure may cause adverse physiological and structural
changes in the pulmonary and cardiovascular systems. Established and
validated metabolomics assays of the lungs, hearts. and blood of young
adult male rats following 1, 3, 8, and 21 days of exposure to ETS
along with day-matched sham control rats (<i>n</i> = 8)
were performed using gas chromatography time-of-flight mass spectrometry,
BinBase database processing, multivariate statistical modeling, and
MetaMapp biochemical mapping. A total of 489 metabolites were measured
in the lung, heart, and blood, of which 142 metabolites were identified
using a standardized metabolite annotation pipeline. Acute and repeated
subchronic exposure to ETS was associated with significant metabolic
changes in the lung related to energy metabolism, defense against
reactive oxygen species, substrate uptake and transport, nucleotide
metabolism, and substrates for structural components of collagen and
membrane lipids. Metabolic changes were least prevalent in heart tissues
but abundant in blood under repeated subchronic ETS exposure. Our
analyses revealed that ETS causes alterations in metabolic networks,
especially those associated with lung structure and function and found
as systemic signals in the blood. The metabolic changes suggest that
ETS exposure may adversely affects the mitochondrial respiratory chain,
lung elasticity, membrane integrity, redox states, cell cycle, and
normal metabolic and physiological functions of the lungs, even after
subchronic ETS exposure