Publications by authors named "Erin S Baker"

94 Publications

Spatial Distribution of Polycyclic Aromatic Hydrocarbon Contaminants after Hurricane Harvey in a Houston Neighborhood.

J Health Pollut 2021 Mar 2;11(29):210308. Epub 2021 Mar 2.

Epidemiology Program, University of Delaware, Newark, Delaware, USA.

Background: Hurricane Harvey made landfall along the Texas Gulf Coast as a Category 4 hurricane on August 25, 2017, producing unprecedented precipitation that devastated coastal areas. Catastrophic flooding in the City of Houston inundated industrial and residential properties resulting in the displacement and transfer of soil, sediment, and debris and heightening existing environmental justice (EJ) concerns.

Objectives: The primary aim of this study was to evaluate the presence, distribution, and potential human health implications of polycyclic aromatic hydrocarbons (PAHs) in a residential neighborhood of Houston, Texas following a major hurricane.

Methods: Concentrations of PAHs in 40 soil samples collected from a residential neighborhood in Houston, Texas were measured. Spatial interpolation was applied to determine the distribution of PAHs. Potential human health risks were evaluated by calculating toxicity equivalency quotients (TEQs) and incremental excess lifetime cancer risk (IELCR).

Results: Total priority PAH concentrations varied across samples (range: 9.7 × 10 ng/g-1.6 × 10 ng/g; mean: 3.0 × 10 ng/g ± 3.6 × 10 standard deviation). Spatial analysis indicated a variable distribution of PAH constituents and concentrations. The IELCR analysis indicated that nine of the 40 samples were above minimum standards.

Conclusions: Findings from this study highlight the need for fine scale soil testing in residential areas as well as the importance of site-specific risk assessment.

Competing Interests: The authors declare no competing financial interests.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5696/2156-9614-11.29.210308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009646PMC
March 2021

From Plants to Ants: Fungal Modification of Leaf Lipids for Nutrition and Communication in the Leaf-Cutter Ant Fungal Garden Ecosystem.

mSystems 2021 Mar 23;6(2). Epub 2021 Mar 23.

The Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, Washington, USA

Lipids are essential to all living organisms, as an energy source, as an important cellular structural component, and as a communication tool. In this study, we used global lipidomic methods to evaluate the lipids in leaf-cutter ant fungal gardens. Leaf-cutter ants and their coevolved fungal cultivar, , are a model mutualistic system. The fungus enzymatically digests fresh plant material that the ants cut and deliver, converting energy and nutrients from plants and providing them to the ants through specialized hyphal swellings called gongylidia. Using combined liquid chromatography, ion mobility spectrometry, and tandem mass spectrometry, we evaluated differences between the molecular species of lipids in the leaf-cutter ant fungal garden ecosystem. This lipidomic study characterized leaves that are fed to the gardens, gongylidia that are produced by the fungus to feed the ants, and spatially resolved regions of the fungal garden through stages of leaf degradation. Lipids containing alpha-linolenic acid (18:3) were enriched in leaves and the top of the gardens but not dominant in the middle or bottom regions. Gongylidia were dominated by lipids containing linoleic acid (18:2). To evaluate the communicative potential of the lipids in fungal gardens, we conducted a behavioral experiment that showed leaf-cutter ants responded differently to 18:3 and 18:2 fatty acids, with aggression toward 18:3 and attraction for 18:2. This work demonstrates the role of lipids in both the transfer of energy and as an interkingdom communication tool in leaf-cutter ant fungal gardens. In this work, we examined the role of lipids in the mutualism between leaf-cutter ants and fungus. These ants cut fresh leaf material, which they provide to their fungal cultivar, that converts energy and nutrients from the plants and provides it to the ants in specialized hyphal swellings called gongylidia. This work constitutes the first example of a global lipidomics study of a symbiotic system and provides insights as to how the fungus modifies plant lipids into a usable source for the ants. Through a behavioral experiment, this work also demonstrates how lipids can be used as an interkingdom communication tool, in this case, as an attractant rather than as a repellant, which is more often seen.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/mSystems.01307-20DOI Listing
March 2021

Ion Mobility Spectrometry Characterization of the Intermediate Hydrogen-Containing Gold Cluster Au(PPh)H.

J Phys Chem Lett 2021 Mar 5;12(10):2502-2508. Epub 2021 Mar 5.

Physical Sciences Division, Pacific Northwest National Laboratory, P.O. Box 999, Richland, Washington 99352, United States.

We employ ion mobility spectrometry and density functional theory to determine the structure of Au(PPh)H (PPh = triphenylphosphine), which was recently identified by high mass resolution mass spectrometry. Experimental ion-neutral collision cross sections represent the momentum transfer between the ionic clusters and gas molecules averaged over the relative thermal velocities of the colliding pair, thereby providing structural insights. Theoretical calculations indicate the geometry of Au(PPh)H is similar to Au(PPh), with three hydrogen atoms bridging two gold atoms and two hydrogen atoms forming single Au-H bonds. Collision-induced dissociation products observed during IMS experiments reveal that smaller hydrogen-containing clusters may be produced through fragmentation of Au(PPh)H. Our findings indicate that hydrogen-containing species like Au(PPh)H act as intermediates in the formation of larger phosphine ligated gold clusters. These results advance the understanding and ability to control the mechanisms of size-selective cluster formation, which is necessary for scalable synthesis of clusters with tailored properties.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jpclett.0c03664DOI Listing
March 2021

Utilizing Ion Mobility-Mass Spectrometry to Investigate the Unfolding Pathway of Cu/Zn Superoxide Dismutase.

Front Chem 2021 9;9:614595. Epub 2021 Feb 9.

Department of Biochemistry, Emory University School of Medicine, Atlanta, GA, United States.

Native mass spectrometry has emerged as a powerful tool for structural biology as it enables the evaluation of molecules as they occur in their physiological conditions. Ion mobility spectrometry-mass spectrometry (IMS-MS) has shown essential in these analyses as it allows the measurement of the shape of a molecule, denoted as its collision cross section (CCS), and mass. The structural information garnered from native IMS-MS provides insight into the tertiary and quaternary structure of proteins and can be used to validate NMR or crystallographic X-ray structures. Additionally, due to the rapid nature (millisecond measurements) and ability of IMS-MS to analyze heterogeneous solutions, it can be used to address structural questions not possible with traditional structural approaches. Herein, we applied multiple solution conditions to systematically denature bovine Cu/Zn-superoxide dismutase (SOD1) and assess its unfolding pathway from the holo-dimer to the holo-monomer, single-metal monomer, and apo-monomer. Additionally, we compared and noted 1-2% agreement between CCS values from both drift tube IMS and trapped IMS for the SOD1 holo-monomer and holo-dimer. The observed CCS values were in excellent agreement with computational CCS values predicted from the homo-dimer crystal structure, showcasing the ability to use both IMS-MS platforms to provide valuable structural information for molecular modeling of protein interactions and structural assessments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fchem.2021.614595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900566PMC
February 2021

Relationships between constituents of energy drinks and beating parameters in human induced pluripotent stem cell (iPSC)-Derived cardiomyocytes.

Food Chem Toxicol 2021 Mar 12;149:111979. Epub 2021 Jan 12.

Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, USA. Electronic address:

Consumption of energy drinks has been associated with adverse cardiovascular effects; however, little is known about the ingredients that may contribute to these effects. We therefore characterized the chemical profiles and in vitro effects of energy drinks and their ingredients on human induced pluripotent stem cell (iPSC)-derived cardiomyocytes, and identified the putative active ingredients using a multivariate prediction model. Energy drinks from 17 widely-available over-the-counter brands were evaluated in this study. The concentrations of six common ingredients (caffeine, taurine, riboflavin, pantothenic acid, adenine, and L-methionine) were quantified by coupling liquid chromatography with a triple quadrupole mass spectrometer for the acquisition of LC-MS/MS spectra. In addition, untargeted analyses for each beverage were performed with a platform combining LC, ion mobility spectrometry and mass spectrometry (LC-IMS-MS) measurements. Approximately 300 features were observed across samples in the untargeted studies, and of these ~100 were identified. In vitro effects of energy drinks and some of their ingredients were then tested in iPSC-derived cardiomyocytes. Data on the beat rate (positive and negative chronotropy), ion channel function (QT prolongation), and cytotoxicity were collected in a dilution series. We found that some of the energy drinks elicited adverse effects on the cardiomyocytes with the most common being an increase in the beat rate, while QT prolongation was also observed at the lowest concentrations. Finally, concentration addition modeling using quantitative data from the 6 common ingredients and multivariate prediction modeling was used to determine potential ingredients responsible for the adverse effects on the cardiomyocytes. These analyses suggested theophylline, adenine, and azelate as possibly contributing to the in vitro effects of energy drinks on QT prolongation in cardiomyocytes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fct.2021.111979DOI Listing
March 2021

From Prevention to Disease Perturbations: A Multi-Omic Assessment of Exercise and Myocardial Infarctions.

Biomolecules 2020 Dec 30;11(1). Epub 2020 Dec 30.

Department of Chemistry, North Carolina State University, Raleigh, NC 27606, USA.

While a molecular assessment of the perturbations and injury arising from diseases is essential in their diagnosis and treatment, understanding changes due to preventative strategies is also imperative. Currently, complex diseases such as cardiovascular disease (CVD), the leading cause of death worldwide, suffer from a limited understanding of how the molecular mechanisms taking place following preventive measures (e.g., exercise) differ from changes occurring due to the injuries caused from the disease (e.g., myocardial infarction (MI)). Therefore, this manuscript assesses lipidomic changes before and one hour after exercise treadmill testing (ETT) and before and one hour after a planned myocardial infarction (PMI) in two separate patient cohorts. Strikingly, unique lipidomic perturbations were observed for these events, as could be expected from their vastly different stresses on the body. The lipidomic results were then combined with previously published metabolomic characterizations of the same patients. This integration provides complementary insights into the exercise and PMI events, thereby giving a more holistic understanding of the molecular changes associated with each.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/biom11010040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824308PMC
December 2020

A Comparative Analysis of Analytical Techniques for Rapid Oil Spill Identification.

Environ Toxicol Chem 2021 Apr 10;40(4):1034-1049. Epub 2021 Mar 10.

Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, Texas, USA.

The complex chemical composition of crude oils presents many challenges for rapid chemical characterization in the case of a spill. A number of approaches are currently used to "fingerprint" petroleum-derived samples. Gas chromatography coupled with mass spectrometry (GC-MS) is the most common, albeit not very rapid, technique; however, with GC-MS alone, it is difficult to resolve the complex substances in crude oils. The present study examined the potential application of ion mobility spectrometry-mass spectrometry (IMS-MS) coupled with chem-informatic analyses as an alternative high-throughput method for the chemical characterization of crude oils. We analyzed 19 crude oil samples from on- and offshore locations in the Gulf of Mexico region in the United States using both GC-MS (biomarkers, gasoline range hydrocarbons, and n-alkanes) and IMS-MS (untargeted analysis). Hierarchical clustering, principal component analysis, and nearest neighbor-based classification were used to examine sample similarity and geographical groupings. We found that direct-injection IMS-MS performed either equally or better than GC-MS in the classification of the origins of crude oils. In addition, IMS-MS greatly increased the sample analysis throughput (minutes vs hours per sample). Finally, a tabletop science-to-practice exercise, utilizing both the GC-MS and IMS-MS data, was conducted with emergency response experts from regulatory agencies and the oil industry. This activity showed that the stakeholders found the IMS-MS data to be highly informative for rapid chemical fingerprinting of complex substances in general and specifically advantageous for accurate and confident source-grouping of crude oils. Collectively, the present study shows the utility of IMS-MS as a technique for rapid fingerprinting of complex samples and demonstrates its advantages over traditional GC-MS-based analyses when used for decision-making in emergency situations. Environ Toxicol Chem 2021;40:1034-1049. © 2020 SETAC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/etc.4961DOI Listing
April 2021

Rapid Characterization of Emerging Per- and Polyfluoroalkyl Substances in Aqueous Film-Forming Foams Using Ion Mobility Spectrometry-Mass Spectrometry.

Environ Sci Technol 2020 12 11;54(23):15024-15034. Epub 2020 Nov 11.

Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, Texas 77845-3424, United States.

Aqueous film-forming foams (AFFF) are mixtures formulated with numerous hydrocarbon- and fluoro-containing surfactants. AFFF use leads to environmental releases of unknown per- and polyfluoroalkyl substances (PFAS). AFFF composition is seldom disclosed, and their use elicits concerns from both regulatory agencies and the public because PFAS are persistent in the environment and potentially associated with adverse health effects. In this study, we demonstrate the use of coupled liquid chromatography, ion mobility spectrometry, and mass spectrometry (LC-IMS-MS) to rapidly characterize both known and unknown PFAS in AFFF. Ten AFFF formulations from seven brands were analyzed using LC-IMS-MS in both negative and positive ion modes. Untargeted analysis of the formulations was followed by feature identification of PFAS-like features utilizing database matching, mass defect and homologous series evaluation, and MS/MS fragmentation experiments. Across the tested AFFF formulations, we identified 33 homologous series; only ten of these homologous series have been previously reported. Among tested AFFF, the FireStopper ( = 85) contained the greatest number of PFAS-like features and Phos-Check contained zero. This work demonstrates that LC-IMS-MS-enabled untargeted analysis of complex formulations, followed by feature identification using data-processing algorithms, can be used for rapid exposure characterization of known and putative PFAS during fire suppression-related contamination events.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.est.0c04798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719402PMC
December 2020

Structural-based connectivity and omic phenotype evaluations (SCOPE): a cheminformatics toolbox for investigating lipidomic changes in complex systems.

Analyst 2020 Nov;145(22):7197-7209

Department of Chemistry, North Carolina State University, Raleigh, NC 27695, USA.

Since its inception, the main goal of the lipidomics field has been to characterize lipid species and their respective biological roles. However, difficulties in both full speciation and biological interpretation have rendered these objectives extremely challenging and as a result, limited our understanding of lipid mechanisms and dysregulation. While mass spectrometry-based advancements have significantly increased the ability to identify lipid species, less progress has been made surrounding biological interpretations. We have therefore developed a Structural-based Connectivity and Omic Phenotype Evaluations (SCOPE) cheminformatics toolbox to aid in these evaluations. SCOPE enables the assessment and visualization of two main lipidomic associations: structure/biological connections and metadata linkages either separately or in tandem. To assess structure and biological relationships, SCOPE utilizes key lipid structural moieties such as head group and fatty acyl composition and links them to their respective biological relationships through hierarchical clustering and grouped heatmaps. Metadata arising from phenotypic and environmental factors such as age and diet is then correlated with the lipid structures and/or biological relationships, utilizing Toxicological Prioritization Index (ToxPi) software. Here, SCOPE is demonstrated for various applications from environmental studies to clinical assessments to showcase new biological connections not previously observed with other techniques.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0an01638aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695036PMC
November 2020

Proteomic assessment of serum biomarkers of longevity in older men.

Aging Cell 2020 11 20;19(11):e13253. Epub 2020 Oct 20.

Oregon Health & Science University, Portland, OR, USA.

The biological bases of longevity are not well understood, and there are limited biomarkers for the prediction of long life. We used a high-throughput, discovery-based proteomics approach to identify serum peptides and proteins that were associated with the attainment of longevity in a longitudinal study of community-dwelling men age ≥65 years. Baseline serum in 1196 men were analyzed using liquid chromatography-ion mobility-mass spectrometry, and lifespan was determined during ~12 years of follow-up. Men who achieved longevity (≥90% expected survival) were compared to those who died earlier. Rigorous statistical methods that controlled for false positivity were utilized to identify 25 proteins that were associated with longevity. All these proteins were in lower abundance in long-lived men and included a variety involved in inflammation or complement activation. Lower levels of longevity-associated proteins were also associated with better health status, but as time to death shortened, levels of these proteins increased. Pathway analyses implicated a number of compounds as important upstream regulators of the proteins and implicated shared networks that underlie the observed associations with longevity. Overall, these results suggest that complex pathways, prominently including inflammation, are linked to the likelihood of attaining longevity. This work may serve to identify novel biomarkers for longevity and to understand the biology underlying lifespan.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/acel.13253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7681066PMC
November 2020

Unveiling molecular signatures of preeclampsia and gestational diabetes mellitus with multi-omics and innovative cheminformatics visualization tools.

Mol Omics 2020 12 23;16(6):521-532. Epub 2020 Sep 23.

Department of Chemistry, North Carolina State University, Raleigh, NC 27695, USA.

To fully enable the development of diagnostic tools and progressive pharmaceutical drugs, it is imperative to understand the molecular changes occurring before and during disease onset and progression. Systems biology assessments utilizing multi-omic analyses (e.g. the combination of proteomics, lipidomics, genomics, etc.) have shown enormous value in determining molecules prevalent in diseases and their associated mechanisms. Herein, we utilized multi-omic evaluations, multi-dimensional analysis methods, and new cheminformatics-based visualization tools to provide an in depth understanding of the molecular changes taking place in preeclampsia (PRE) and gestational diabetes mellitus (GDM) patients. Since PRE and GDM are two prevalent pregnancy complications that result in adverse health effects for both the mother and fetus during pregnancy and later in life, a better understanding of each is essential. The multi-omic evaluations performed here provide new insight into the end-stage molecular profiles of each disease, thereby supplying information potentially crucial for earlier diagnosis and treatments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0mo00074dDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736332PMC
December 2020

Enhanced protocol for quantitative N-linked glycomics analysis using Individuality Normalization when Labeling with Isotopic Glycan Hydrazide Tags (INLIGHT)™.

Anal Bioanal Chem 2020 Nov 26;412(27):7569-7579. Epub 2020 Aug 26.

Department of Chemistry, North Carolina State University, Raleigh, NC, 27695, USA.

The analysis of N-linked glycans using liquid chromatography and mass spectrometry (LC-MS) presents significant challenges, particularly owing to their hydrophilic nature. To address these difficulties, a variety of derivatization methods have been developed to facilitate improved ionization and detection sensitivity. One such method, the Individuality Normalization when Labeling with Isotopic Glycan Hydrazide Tags (INLIGHT)™ strategy for labeling glycans, has previously been utilized in the analysis of N- and O-linked glycans in biological samples. To assess the maximum sensitivity and separability of the INLIGHT™ preparation and analysis pipeline, several critical steps were investigated. First, recombinant and nonrecombinant sources of PNGase F were compared to assess variations in the released glycans. Second, modifications in the INLIGHT™ derivatization step were evaluated including temperature optimization, solvent composition changes, reaction condition length and tag concentration. Optimization of the modified method resulted in 20-100 times greater peak areas for the detected N-linked glycans in fetuin and horseradish peroxidase compared with the standard method. Furthermore, the identification of low-abundance glycans, such as (Fuc)(Gal)(GlcNAc)(Man)(NeuAc) and (Gal)(GlcNAc)(Man)(NeuAc), was possible. Finally, the optimal LC setup for the INLIGHT™ derivatized N-linked glycan analyses was found to be a C18 reverse-phase (RP) column with mobile phases typical of RPLC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00216-020-02892-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541788PMC
November 2020

Temporal and spatial analysis of per and polyfluoroalkyl substances in surface waters of Houston ship channel following a large-scale industrial fire incident.

Environ Pollut 2020 Oct 12;265(Pt B):115009. Epub 2020 Jun 12.

Interdisciplinary Faculty of Toxicology, Texas A&M University, College Station, TX, USA; Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, USA. Electronic address:

Firefighting foams contain per- and polyfluoroalkyl substances (PFAS) - a class of compounds widely used as surfactants. PFAS are persistent organic pollutants that have been reported in waterways and drinking water systems across the United States. These substances are of interest to both regulatory agencies and the general public because of their persistence in the environment and association with adverse health effects. PFAS can be released in large quantities during industrial incidents because they are present in most firefighting foams used to suppress chemical fires; however, little is known about persistence of PFAS in public waterways after such events. In response to large-scale fires at Intercontinental Terminal Company (ITC) in Houston, Texas in March 2019, almost 5 million liters of class B firefighting foams were used. Much of this material flowed into the Houston Ship Channel and Galveston Bay (HSC/GB) and concerns were raised about the levels of PFAS in these water bodies that have commercial and recreational uses. To evaluate the impact of the ITC incident response on PFAS levels in HSC/GB, we collected 52 surface water samples from 12 locations over a 6-month period after the incident. Samples were analyzed using liquid chromatography-mass spectrometry to evaluate 27 PFAS, including perfluorocarboxylic acids, perfluorosulfonates and fluorotelomers. Among PFAS that were evaluated, 6:2 FTS and PFOS were detected at highest concentrations. Temporal and spatial profiles of PFAS were established; we found a major peak in the level of many PFAS in the days and weeks after the incident and a gradual decline over several months with patterns consistent with the tide- and wave-associated water movements. This work documents the impact of a large-scale industrial fire, on the environmental levels of PFAS, establishes a baseline concentration of PFAS in HSC/GB, and highlights the critical need for development of PFAS water quality standards.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envpol.2020.115009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857671PMC
October 2020

Rapid Characterization of Per- and Polyfluoroalkyl Substances (PFAS) by Ion Mobility Spectrometry-Mass Spectrometry (IMS-MS).

Anal Chem 2020 03 24;92(6):4427-4435. Epub 2020 Feb 24.

Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695, United States.

Per- and polyfluoroalkyl substances (PFAS) are an ensemble of persistent organic pollutants of global interest because of their associations with adverse health outcomes. Currently, environmental PFAS pollution is prolific as a result of the widespread manufacturing of these compounds and their chemical persistence. In this work, we demonstrate the advantages of adding ion mobility spectrometry (IMS) separation to existing LC-MS workflows for PFAS analysis. Using a commercially available drift tube IMS-MS, we characterized PFAS species and isomeric content in both analytical standards and environmental water samples. Molecular trendlines based on intrinsic mass and structural relationships were also explored for individual PFAS subclasses (. PFSA, PFCA, etc.). Results from rapid IMS-MS analyses provided a link between mass and collision cross sections (CCS) for specific PFAS families and are linked to compositional differences in molecular structure. In addition, CCS values provide additional confidence of annotating prioritized features in untargeted screening studies for potential environmental pollutants. Results from this study show that the IMS separation provides novel information to support traditional LC-MS PFAS analyses and will greatly benefit the evaluation of unknown pollutants in future environmental studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.analchem.9b05364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7173758PMC
March 2020

Coupling IR-MALDESI with Drift Tube Ion Mobility-Mass Spectrometry for High-Throughput Screening and Imaging Applications.

J Am Soc Mass Spectrom 2020 Mar 11;31(3):642-650. Epub 2020 Feb 11.

FTMS Laboratory for Human Health Research, Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695, United States.

Because of its high degree of selectivity and chemical resolution, mass spectrometry (MS) is rapidly becoming the analytical method of choice for high-throughput evaluations and clinical diagnostics. While advances in MS resolving power have increased by an order of magnitude over the past decade, advances in sample introduction are still needed for high-throughput screening applications where the time frame of chromatographic separation would limit the duty cycle. Infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) is an ambient ionization source that has been shown to be applicable for direct analyses and mass spectrometry imaging (MSI) of complex biological samples in a high-throughput manner. To increase a range of detectable features in IR-MALDESI experiments, we integrated the home-built ion source with a commercially available drift tube ion mobility spectrometer-mass spectrometer (IMS-MS) and analyzed small polar molecules, lipids, carbohydrates, and intact proteins. We also describe in detail how the pulsed ionization source was synchronized with IMS-MS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/jasms.9b00081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7263366PMC
March 2020

Ion Mobility Spectrometry and the Omics: Distinguishing Isomers, Molecular Classes and Contaminant Ions in Complex Samples.

Trends Analyt Chem 2019 Jul 29;116:292-299. Epub 2019 Apr 29.

Department of Chemistry, NC State University, Raleigh, NC.

Ion mobility spectrometry (IMS) is a widely used analytical technique providing rapid gas phase separations. IMS alone is useful, but its coupling with mass spectrometry (IMS-MS) and various front-end separation techniques has greatly increased the molecular information achievable from different omic analyses. IMS-MS analyses are specifically gaining attention for improving metabolomic, lipidomic, glycomic, proteomic and exposomic analyses by increasing measurement sensitivity (e.g. S/N ratio), reducing the detection limit, and amplifying peak capacity. Numerous studies including national security-related analyses, disease screenings and environmental evaluations are illustrating that IMS-MS is able to extract information not possible with MS alone. Furthermore, IMS-MS has shown great utility in salvaging molecular information for low abundance molecules of interest when high concentration contaminant ions are present in the sample by reducing detector suppression. This review highlights how IMS-MS is currently being used in omic analyses to distinguish structurally similar molecules, isomers, molecular classes and contaminant ions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.trac.2019.04.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6887105PMC
July 2019

Utilizing Drift Tube Ion Mobility Spectrometry for the Evaluation of Metabolites and Xenobiotics.

Methods Mol Biol 2020 ;2084:35-54

Department of Chemistry, North Carolina State University, Raleigh, NC, USA.

Metabolites and xenobiotics are small molecules with a molecular weight that often falls below 600 Da. Over the last few decades, multiple small molecule databases have been curated listing structures, masses, and fragmentation spectra possible in metabolomic and exposomic measurements. To date only a small portion of the spectra in these databases are experimentally derived due to the high expense of obtaining, synthesizing, and analyzing standards. A vast majority of spectra have thus been created using theoretical programs to fit the available experimental data. The errors associated with theoretical data have however caused problems with current small molecule identifications, and accurate quantitation as searching the databases using just one or two analysis dimensions (i.e., chromatography retention times and mass spectrometry (MS) m/z values) results in numerous annotations for each experimental feature. Additional analysis dimensions are therefore needed to better annotate and identify small molecules. Drift tube ion mobility spectrometry coupled with MS (DTIMS-MS) is a promising technique to address this challenge as it is able to perform rapid structural evaluations of small molecules in complex matrices by assessing the collision cross section values for each in addition to their m/z values. The use of IMS in conjunction with other separation techniques such as gas or liquid chromatography and MS has therefore enabled more accurate identifications for the small molecules present in complex biological and environmental samples. Here, we present a review of relevant parameter considerations for DTIMS application with emphasis on xenobiotics and metabolomics isomer separations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/978-1-0716-0030-6_2DOI Listing
December 2020

Ion Mobility Spectrometry: Fundamental Concepts, Instrumentation, Applications, and the Road Ahead.

J Am Soc Mass Spectrom 2019 Nov 6;30(11):2185-2195. Epub 2019 Sep 6.

Department of Chemistry, North Carolina State University, Raleigh, NC, 27695, USA.

Ion mobility spectrometry (IMS) is a rapid separation technique that has experienced exponential growth as a field of study. Interfacing IMS with mass spectrometry (IMS-MS) provides additional analytical power as complementary separations from each technique enable multidimensional characterization of detected analytes. IMS separations occur on a millisecond timescale, and therefore can be readily nested into traditional GC and LC/MS workflows. However, the continual development of novel IMS methods has generated some level of confusion regarding the advantages and disadvantages of each. In this critical insight, we aim to clarify some common misconceptions for new users in the community pertaining to the fundamental concepts of the various IMS instrumental platforms (i.e., DTIMS, TWIMS, TIMS, FAIMS, and DMA), while addressing the strengths and shortcomings associated with each. Common IMS-MS applications are also discussed in this review, such as separating isomeric species, performing signal filtering for MS, and incorporating collision cross-section (CCS) values into both targeted and untargeted omics-based workflows as additional ion descriptors for chemical annotation. Although many challenges must be addressed by the IMS community before mobility information is collected in a routine fashion, the future is bright with possibilities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13361-019-02288-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832852PMC
November 2019

Perspectives on Data Analysis in Metabolomics: Points of Agreement and Disagreement from the 2018 ASMS Fall Workshop.

J Am Soc Mass Spectrom 2019 Oct 22;30(10):2031-2036. Epub 2019 Aug 22.

Departments of Chemistry and Medicine, Washington University in St. Louis, St. Louis, MO, USA.

In November 2018, the American Society for Mass Spectrometry hosted the Annual Fall Workshop on informatic methods in metabolomics. The Workshop included sixteen lectures presented by twelve invited speakers. The focus of the talks was untargeted metabolomics performed with liquid chromatography/mass spectrometry. In this review, we highlight five recurring topics that were covered by multiple presenters: (i) data sharing, (ii) artifacts and contaminants, (iii) feature degeneracy, (iv) database organization, and (v) requirements for metabolite identification. Our objective here is to present viewpoints that were widely shared among participants, as well as those in which varying opinions were articulated. We note that most of the presenting speakers employed different data processing software, which underscores the diversity of informatic programs currently being used in metabolomics. We conclude with our thoughts on the potential role of reference datasets as a step towards standardizing data processing methods in metabolomics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13361-019-02295-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7310669PMC
October 2019

Folding and Assembly of Short α, β, γ-Hybrid Peptides: Minor Variations in Sequence and Drastic Differences in Higher-Level Structures.

J Am Chem Soc 2019 09 26;141(36):14239-14248. Epub 2019 Aug 26.

Department of Chemistry , University at Buffalo, The State University of New York , Buffalo , New York 14260 , United States.

Multilevel protein structures typically involve polypeptides of sufficient lengths. Here we report the folding and assembly of seven short tetrapeptides sharing the same types of α-, β-, and aromatic γ-amino acid residues. These are two sets of hybrid peptides, with three members in one set and four in the other, having complementary hydrogen-bonding sequences that were hypothesized to pair into linear H-bonded duplexes. However, instead of undergoing the anticipated pairing, the initially examined three oligomers, and or , differing only in their central αβ hybrid dipeptide sequence, do not associate with each other and exhibit distinctly different folding behavior. Experiments based on NMR and mass spectrometry, along with computational studies and systematic inference, reveal that oligomer folds into an expanded β-turn containing an unusual hybrid α/β-amino acid sequence composed of glycine and β-alanine, two α- and β-amino acid residues that are conformationally most flexible, and peptides and adopt a noncanonical, extended helical conformation and dimerize into double helices undergoing rapid conformational exchange or helix inversion. The different central dipeptide sequences, αβ vs βα, result in drastically different intramolecular H-bonding patterns that are responsible for the observed folding behavior of and . The revealed turn and double helix have few natural or synthetic counterparts, and provide novel and unique folding prototypes based on which chiral α- and β-amino acids are incorporated. The resultant derivatives , , , and follow the same folding and assembling behavior and demonstrate the generality of this system with the formation of expanded β-turns and double helices with enhanced folding stabilities, hampered helix inversion, as well as defined and dominant helical sense. This work has demonstrated the unique capability of synthetic foldamers in generating structures with fascinating folding and assembling behavior. The revealed systems offer ample opportunity for further structural optimization and applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/jacs.9b06094DOI Listing
September 2019

Evaluating the structural complexity of isomeric bile acids with ion mobility spectrometry.

Anal Bioanal Chem 2019 Jul 16;411(19):4673-4682. Epub 2019 May 16.

Department of Chemistry, North Carolina State University, 2620 Yarbrough Dr., Campus Box 8204, Raleigh, NC, 27695, USA.

Bile acids (BAs) play an integral role in digestion through the absorption of nutrients, emulsification of fats and fat-soluble vitamins, and maintenance of cholesterol levels. Metabolic disruption, diabetes, colorectal cancer, and numerous other diseases have been linked with BA disruption, making improved BA analyses essential. To date, most BA measurements are performed using liquid chromatography separations in conjunction with mass spectrometry measurements (LC-MS). However, 10-40 min LC gradients are often used for BA analyses and these may not even be sufficient for distinguishing all the important isomers present in the human body. Ion mobility spectrometry (IMS) is a promising tool for BA evaluations due to its ability to quickly separate isomeric molecules with subtle structural differences. In this study, we utilized drift tube IMS (DTIMS) coupled with MS to characterize 56 different unlabeled BA standards and 16 deuterated versions. In the DTIMS-MS analyses of 12 isomer groups, BAs with smaller m/z values were easily separated in either their deprotonated or sodiated forms (or both). However, as the BAs grew in m/z value, they became more difficult to separate with two isomer groups being inseparable. Metal ions such as copper and zinc were then added to the overlapping BAs, and due to different binding sites, the resulting complexes were separable. Thus, the rapid structural measurements possible with DTIMS-MS show great potential for BAs measurements with and without prior LC separations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00216-019-01869-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6612315PMC
July 2019

Predicting Ion Mobility Collision Cross-Sections Using a Deep Neural Network: DeepCCS.

Anal Chem 2019 04 1;91(8):5191-5199. Epub 2019 Apr 1.

Big Data Research Centre , Université Laval , Québec City G1 V 0A6 , Canada.

Untargeted metabolomic measurements using mass spectrometry are a powerful tool for uncovering new small molecules with environmental and biological importance. The small molecule identification step, however, still remains an enormous challenge due to fragmentation difficulties or unspecific fragment ion information. Current methods to address this challenge are often dependent on databases or require the use of nuclear magnetic resonance (NMR), which have their own difficulties. The use of the gas-phase collision cross section (CCS) values obtained from ion mobility spectrometry (IMS) measurements were recently demonstrated to reduce the number of false positive metabolite identifications. While promising, the amount of empirical CCS information currently available is limited, thus predictive CCS methods need to be developed. In this article, we expand upon current experimental IMS capabilities by predicting the CCS values using a deep learning algorithm. We successfully developed and trained a prediction model for CCS values requiring only information about a compound's SMILES notation and ion type. The use of data from five different laboratories using different instruments allowed the algorithm to be trained and tested on more than 2400 molecules. The resulting CCS predictions were found to achieve a coefficient of determination of 0.97 and median relative error of 2.7% for a wide range of molecules. Furthermore, the method requires only a small amount of processing power to predict CCS values. Considering the performance, time, and resources necessary, as well as its applicability to a variety of molecules, this model was able to outperform all currently available CCS prediction algorithms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.analchem.8b05821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6628689PMC
April 2019

Challenges in Identifying the Dark Molecules of Life.

Annu Rev Anal Chem (Palo Alto Calif) 2019 06 18;12(1):177-199. Epub 2019 Mar 18.

School of Chemistry and Biochemistry, Georgia Institute of Technology and Petit Institute for Biochemistry and Bioscience, Atlanta, Georgia 30332, USA; email:

Metabolomics is the study of the metabolome, the collection of small molecules in living organisms, cells, tissues, and biofluids. Technological advances in mass spectrometry, liquid- and gas-phase separations, nuclear magnetic resonance spectroscopy, and big data analytics have now made it possible to study metabolism at an omics or systems level. The significance of this burgeoning scientific field cannot be overstated: It impacts disciplines ranging from biomedicine to plant science. Despite these advances, the central bottleneck in metabolomics remains the identification of key metabolites that play a class-discriminant role. Because metabolites do not follow a molecular alphabet as proteins and nucleic acids do, their identification is much more time consuming, with a high failure rate. In this review, we critically discuss the state-of-the-art in metabolite identification with specific applications in metabolomics and how technologies such as mass spectrometry, ion mobility, chromatography, and nuclear magnetic resonance currently contribute to this challenging task.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-anchem-061318-114959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6716371PMC
June 2019

Utilizing ion mobility spectrometry and mass spectrometry for the analysis of polycyclic aromatic hydrocarbons, polychlorinated biphenyls, polybrominated diphenyl ethers and their metabolites.

Anal Chim Acta 2018 Dec 2;1037:265-273. Epub 2018 Mar 2.

Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, United States. Electronic address:

Polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are persistent environmental pollutants originating from incomplete combustion of organic materials and synthetic sources. PAHs, PCBs, and PBDEs have all been shown to have a significant effect on human health with correlations to cancer and other diseases. Therefore, measuring the presence of these xenobiotics in the environment and human body is imperative for assessing their health risks. To date, their analyses require both gas chromatography and liquid chromatography separations in conjunction with mass spectrometry measurements for detection of both the parent molecules and their hydroxylated metabolites, making their studies extremely time consuming. In this work, we characterized PAHs, PCBs, PBDEs and their hydroxylated metabolites using ion mobility spectrometry coupled with mass spectrometry (IMS-MS) and in combination with different ionization methods including electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI) and atmospheric pressure photoionization (APPI). The collision cross section and m/z trend lines derived from the IMS-MS analyses displayed distinct trends for each molecule type. Additionally, the rapid isomeric and molecular separations possible with IMS-MS showed great promise for quickly distinguishing the parent and metabolized PAH, PCB, and PDBE molecules in complex environmental and biological samples.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.aca.2018.02.054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6223027PMC
December 2018

Unraveling the isomeric heterogeneity of glycans: ion mobility separations in structures for lossless ion manipulations.

Chem Commun (Camb) 2018 Oct 28;54(83):11701-11704. Epub 2018 Sep 28.

Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA.

To address the challenges associated with glycan analyses, we have implemented a structures for lossless ion manipulations (SLIM) serpentine ultra-long path with extended routing (SUPER) ion mobility-mass spectrometry (i.e. SLIM SUPER IM-MS) platform to achieve much higher resolution of isomeric glycoforms. We have demonstrated the potential of this platform as a future component of the glycomics toolbox.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c8cc06966bDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6191335PMC
October 2018

Application of multiplexed ion mobility spectrometry towards the identification of host protein signatures of treatment effect in pulmonary tuberculosis.

Tuberculosis (Edinb) 2018 09 18;112:52-61. Epub 2018 Jul 18.

Division of Pulmonary and Critical Care Medicine, University of California San Francisco, San Francisco, CA, USA.

Rationale: The monitoring of TB treatments in clinical practice and clinical trials relies on traditional sputum-based culture status indicators at specific time points. Accurate, predictive, blood-based protein markers would provide a simpler and more informative view of patient health and response to treatment.

Objective: We utilized sensitive, high throughput multiplexed ion mobility-mass spectrometry (IM-MS) to characterize the serum proteome of TB patients at the start of and at 8 weeks of rifamycin-based treatment. We sought to identify treatment specific signatures within patients as well as correlate the proteome signatures to various clinical markers of treatment efficacy.

Methods: Serum samples were collected from 289 subjects enrolled in CDC TB Trials Consortium Study 29 at time of enrollment and at the end of the intensive phase (after 40 doses of TB treatment). Serum proteins were immunoaffinity-depleted of high abundant components, digested to peptides and analyzed for data acquisition utilizing a unique liquid chromatography IM-MS platform (LC-IM-MS). Linear mixed models were utilized to identify serum protein changes in the host response to antibiotic treatment as well as correlations with culture status end points.

Results: A total of 10,137 peptides corresponding to 872 proteins were identified, quantified, and used for statistical analysis across the longitudinal patient cohort. In response to TB treatment, 244 proteins were significantly altered. Pathway/network comparisons helped visualize the interconnected proteins, identifying up regulated (lipid transport, coagulation cascade, endopeptidase activity) and down regulated (acute phase) processes and pathways in addition to other cross regulated networks (inflammation, cell adhesion, extracellular matrix). Detection of possible lung injury serum proteins such as HPSE, significantly downregulated upon treatment. Analyses of microbiologic data over time identified a core set of serum proteins (TTHY, AFAM, CRP, RET4, SAA1, PGRP2) which change in response to treatment and also strongly correlate with culture status. A similar set of proteins at baseline were found to be predictive of week 6 and 8 culture status.

Conclusion: A comprehensive host serum protein dataset reflective of TB treatment effect is defined. A repeating set of serum proteins (TTHY, AFAM, CRP, RET4, SAA1, PGRP2, among others) were found to change significantly in response to treatment, to strongly correlate with culture status, and at baseline to be predictive of future culture conversion. If validated in cohorts with long term follow-up to capture failure and relapse of TB, these protein markers could be developed for monitoring of treatment in clinical trials and in patient care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tube.2018.07.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6181582PMC
September 2018

Cell type-resolved human lung lipidome reveals cellular cooperation in lung function.

Sci Rep 2018 09 7;8(1):13455. Epub 2018 Sep 7.

Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, 99352, USA.

Cell type-resolved proteome analyses of the brain, heart and liver have been reported, however a similar effort on the lipidome is currently lacking. Here we applied liquid chromatography-tandem mass spectrometry to characterize the lipidome of major lung cell types isolated from human donors, representing the first lipidome map of any organ. We coupled this with cell type-resolved proteomics of the same samples (available at Lungmap.net). Complementary proteomics analyses substantiated the functional identity of the isolated cells. Lipidomics analyses showed significant variations in the lipidome across major human lung cell types, with differences most evident at the subclass and intra-subclass (i.e. total carbon length of the fatty acid chains) level. Further, lipidomic signatures revealed an overarching posture of high cellular cooperation within the human lung to support critical functions. Our complementary cell type-resolved lipid and protein datasets serve as a rich resource for analyses of human lung function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-018-31640-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6128932PMC
September 2018

Distinguishing enantiomeric amino acids with chiral cyclodextrin adducts and structures for lossless ion manipulations.

Electrophoresis 2018 12 17;39(24):3148-3155. Epub 2018 Sep 17.

Biological Sciences Division, Pacific Northwest National Laboratory, Richland, USA.

Enantiomeric molecular evaluations remain an enormous challenge for current analytical techniques. To date, derivatization strategies and long separation times are generally required in these studies, and the development and implementation of new approaches are needed to increase speed and distinguish currently unresolvable compounds. Herein, we describe a method using chiral cyclodextrin adducts and structures for lossless ion manipulations (SLIM) and serpentine ultralong path with extended routing (SUPER) ion mobility (IM) to achieve rapid, high resolution separations of d and l enantiomeric amino acids. In the analyses, a chiral cyclodextrin is added to each sample. Two cyclodextrins were found to complex each amino acid molecule (i.e. potentially sandwiching the amino acid in their cavities) and forming host-guest noncovalent complexes that were distinct for each d and l amino acid pair studied and thus separable with IM in SLIM devices. The SLIM was also used to accumulate much larger ion populations than previously feasible for evaluation and therefore allow enantiomeric measurements of higher sensitivity, with gains in resolution from our ultralong path separation capabilities, than previously reported by any other IM-based approach.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/elps.201800294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6294673PMC
December 2018

Improved Sensitivity and Separations for Phosphopeptides using Online Liquid Chromotography Coupled with Structures for Lossless Ion Manipulations Ion Mobility-Mass Spectrometry.

Anal Chem 2018 09 29;90(18):10889-10896. Epub 2018 Aug 29.

Biological Sciences Division , Pacific Northwest National Laboratory , Richland , Washington 99352 , United States.

Phosphoproteomics greatly augments proteomics and holds tremendous potential for insights into the modulation of biological systems for various disease states. However, numerous challenges hinder conventional methods in terms of measurement sensitivity, throughput, quantification, and capabilities for confident phosphopeptide and phosphosite identification. In this work, we report the first example of integrating structures for lossless ion manipulations ion mobility-mass spectrometry (SLIM IM-MS) with online reversed-phase liquid chromatography (LC) to evaluate its potential for addressing the aforementioned challenges. A mixture of 51 heavy-labeled phosphopeptides was analyzed with a SLIM IM module having integrated ion accumulation and long-path separation regions. The SLIM IM-MS provided limits of detection as low as 50-100 pM (50-100 amol/μL) for several phosphopeptides, with the potential for significant further improvements. In addition, conventionally problematic phosphopeptide isomers could be resolved following an 18 m SLIM IM separation. The 2-D LC-IM peak capacity was estimated as ∼9000 for a 90 min LC separation coupled to an 18 m SLIM IM separation, considerably higher than LC alone and providing a basis for both improved identification and quantification, with additional gains projected with the future use of longer path SLIM IM separations. Thus, LC-SLIM IM-MS offers great potential for improving the sensitivity, separation, and throughput of phosphoproteomics analyses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.analchem.8b02397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6211290PMC
September 2018