xMSannotator: An R Package for Network-Based Annotation of High-Resolution Metabolomics Data

Improved analytical technologies and data extraction algorithms enable detection of >10 000 reproducible signals by liquid chromatography–high-resolution mass spectrometry, creating a bottleneck in chemical identification. In principle, measurement of more than one million chemicals would be possible if algorithms were available to facilitate utilization of the raw mass spectrometry data, especially low-abundance metabolites. Here we describe an automated computational framework to annotate ions for possible chemical identity using a multistage clustering algorithm in which metabolic pathway associations are used along with intensity profiles, retention time characteristics, mass defect, and isotope/adduct patterns. The algorithm uses high-resolution mass spectrometry data for a series of samples with common properties and publicly available chemical, metabolic, and environmental databases to assign confidence levels to annotation results. Evaluation results show that the algorithm achieves an F1-measure of 0.8 for a data set with known targets and is more robust than previously reported results for cases when database size is much greater than the actual number of metabolites. MS/MS evaluation of a set of randomly selected 210 metabolites annotated using xMSannotator in an untargeted metabolomics human data set shows that 80% of features with high or medium confidence scores have ion dissociation patterns consistent with the xMSannotator annotation. The algorithm has been incorporated into an R package, xMSannotator, which includes utilities for querying local or online databases such as ChemSpider, KEGG, HMDB, T3DB, and LipidMaps

ADAP-GC 3.2: Graphical Software Tool for Efficient Spectral Deconvolution of Gas Chromatography–High-Resolution Mass Spectrometry Metabolomics Data

ADAP-GC is an automated computational workflow for extracting metabolite information from raw, untargeted gas chromatography–mass spectrometry metabolomics data. Deconvolution of coeluting analytes is a critical step in the workflow, and the underlying algorithm is able to extract fragmentation mass spectra of coeluting analytes with high accuracy. However, its latest version ADAP-GC 3.0 was not user-friendly. To make ADAP-GC easier to use, we have developed ADAP-GC 3.2 and describe here the improvements on three aspects. First, all of the algorithms in ADAP-GC 3.0 written in R have been replaced by their analogues in Java and incorporated into MZmine 2 to make the workflow user-friendly. Second, the clustering algorithm DBSCAN has replaced the original hierarchical clustering to allow faster spectral deconvolution. Finally, algorithms originally developed for constructing extracted ion chromatograms (EICs) and detecting EIC peaks from LC–MS data are incorporated into the ADAP-GC workflow, allowing the latter to process high mass resolution data. Performance of ADAP-GC 3.2 has been evaluated using unit mass resolution data from standard-mixture and urine samples. The identification and quantitation results were compared with those produced by ADAP-GC 3.0, AMDIS, AnalyzerPro, and ChromaTOF. Identification results for high mass resolution data derived from standard-mixture samples are presented as well

Human Suction Blister Fluid Composition Determined Using High-Resolution Metabolomics

Interstitial fluid (ISF) surrounds the cells and tissues of the body. Since ISF has molecular components similar to plasma, as well as compounds produced locally in tissues, it may be a valuable source of biomarkers for diagnostics and monitoring. However, there has not been a comprehensive study to determine the metabolite composition of ISF and to compare it to plasma. In this study, the metabolome of suction blister fluid (SBF), which largely consists of ISF, collected from 10 human volunteers was analyzed using untargeted high-resolution metabolomics (HRM). A wide range of metabolites were detected in SBF, including amino acids, lipids, nucleotides, and compounds of exogenous origin. Various systemic and skin-derived metabolite biomarkers were elevated or found uniquely in SBF, and many other metabolites of clinical and physiological significance were well correlated between SBF and plasma. In sum, using untargeted HRM profiling, this study shows that SBF can be a valuable source of information about metabolites relevant to human health

Human Suction Blister Fluid Composition Determined Using High-Resolution Metabolomics

Interstitial fluid (ISF) surrounds the cells and tissues of the body. Since ISF has molecular components similar to plasma, as well as compounds produced locally in tissues, it may be a valuable source of biomarkers for diagnostics and monitoring. However, there has not been a comprehensive study to determine the metabolite composition of ISF and to compare it to plasma. In this study, the metabolome of suction blister fluid (SBF), which largely consists of ISF, collected from 10 human volunteers was analyzed using untargeted high-resolution metabolomics (HRM). A wide range of metabolites were detected in SBF, including amino acids, lipids, nucleotides, and compounds of exogenous origin. Various systemic and skin-derived metabolite biomarkers were elevated or found uniquely in SBF, and many other metabolites of clinical and physiological significance were well correlated between SBF and plasma. In sum, using untargeted HRM profiling, this study shows that SBF can be a valuable source of information about metabolites relevant to human health

MS/MS fragmentation spectra show positive identification of resolvin D1 (RvD1), resolvin D2 (RvD2), and aspirin-triggered resolvin D1 (AT-RvD1) in plasma from subjects with TB disease.

<p>Metabololipidomics analytical methods that incorporated high-resolution liquid chromatography coupled with tandem mass spectroscopy (LC-MS/MS, ABI 5500, see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0108854#s2" target="_blank">methods</a>) were used to verify these DHA-derived specialized pro-resolving lipid mediators <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0108854#pone.0108854-Dalli1" target="_blank">[31]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0108854#pone.0108854-Yang1" target="_blank">[33]</a>.</p

Linkage of trehalose-6-mycolate, phosphatidylinositol and the D-series resolvin metabolite(s) in plasma of patients without or with MDR-TB.

<p>Linkage of trehalose-6-mycolate, phosphatidylinositol and the D-series resolvin metabolite(s) in plasma of patients without or with MDR-TB.</p

Significant metabolites that distinguish TB patients from household contacts.

<p>(A) Two-way hierarchical cluster analysis (HCA) using C18 chromatography shows 8 clusters of metabolites from human plasma and illustrates the patterns distinguishing those with active TB from household contacts without evidence of TB disease. The 17 subjects with TB disease (TB; shown in green) and the 17 household contacts (HC; shown in red) are shown along the x-axis. (B) Pie chart depicts chemical classes of the 61 significant metabolites from panel 2A according to high-resolution matches to metabolite databases <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0108854#pone.0108854-Jones1" target="_blank">[6]</a>.</p

Demographic characteristics of individuals with TB disease and their asymptomatic household contacts.

<p>Demographic characteristics of individuals with TB disease and their asymptomatic household contacts.</p