Data sources and statistics for estimation of population attributable fractions (PAFs) in monozygotic twins.

<p>Data sources and statistics for estimation of population attributable fractions (PAFs) in monozygotic twins.</p

Population attributable fractions (PAFs) for 28 disease phenotypes estimated from studies of monozygotic twins.

<p>Sources of data and statistics are summarized in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0154387#pone.0154387.t002" target="_blank">Table 2</a>.</p

Global deaths attributed to exposure-risk factors for chronic diseases.

<p>Global deaths attributed to exposure-risk factors for chronic diseases.</p

Numbers of Western-European deaths in 2000 estimated for ischemic heart disease and nine cancer types (1.53 million total deaths from these causes).

<p>The contributions attributed to genetics plus shared exposures are based on the population attributable fractions (PAFs) estimated from Western European monozygotic twins (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0154387#pone.0154387.t002" target="_blank">Table 2</a>).</p

Antibody Enrichment and Mass Spectrometry of Albumin-Cys34 Adducts

Untargeted analyses of tryptic peptides of human serum albumin (HSA) have been used to investigate unknown exposures to reactive electrophiles (adductomics). To reduce the complexity of the analytical matrix and thereby enhance identification of adducts by liquid chromatography-high-resolution mass spectrometry (LC-HRMS), a polyclonal anti-T3 antibody was designed to capture Cys34 adducts in tryptic digests of HSA (T3 is the third largest tryptic peptide). Epitopes were selected from sequences at both <i>C</i>- and <i>N</i>-termini based on the three-dimensional structure of the T3 peptide to minimize the influence of modified Cys34 residues. The assay was simplified by attaching magnetic beads to the anti-T3 antibody. When applied to commercial HSA and to plasma samples from healthy humans and analyzed by LC-HRMS, antibody treatment greatly reduced the background of non-T3 peptides in the sample matrix. Although other lipophilic HSA peptides were still present, presumably due to nonspecific binding to the antibody-magnetic-bead surfaces, their concentrations in antibody-treated samples were reduced about 6-fold compared to the same samples that had not been treated with the antibody. Analysis of antibody-enriched HSA digests from human plasma samples revealed 10 modified T3 peptides of which 8 were identified from accurate masses. Identified peptides included Cys34 oxidation and cysteinylation products and modifications representing losses of water and Lys and transpeptidation of Arg

Concentrations of Persistent Organic Pollutants in California Children’s Whole Blood and Residential Dust

We evaluated relationships between persistent organic pollutant (POP) levels in the blood of children with leukemia and POP levels in dust from their household vacuum cleaners. Blood and dust were collected from participants of the California Childhood Leukemia Study at various intervals from 1999 to 2007 and analyzed for two polybrominated diphenyl ethers (PBDEs), two polychlorinated biphenyls (PCBs), and two organochlorine pesticides using gas chromatography–mass spectrometry. Due to small blood sample volumes (100 μL), dichlorodiphenyldichloroethylene (DDE) and BDE-153 were the only analytes with detection frequencies above 70%. For each analyte, depending on its detection frequency, a multivariable linear or logistic regression model was used to evaluate the relationship between POP levels in blood and dust, adjusting for child’s age, ethnicity, and breastfeeding duration; mother’s country of origin; household annual income; and blood sampling date. In linear regression, concentrations of BDE-153 in blood and dust were positively associated; whereas, DDE concentrations in blood were positively associated with breastfeeding, maternal birth outside the U.S., and Hispanic ethnicity, but not with corresponding dust-DDE concentrations. The probability of PCB-153 detection in a child’s blood was marginally associated with dust-PCB-153 concentrations (<i>p</i> = 0.08) in logistic regression and significantly associated with breastfeeding. Our findings suggest that dust ingestion is a source of children’s exposure to certain POPs

Normalized sensitivity coefficients for the end-exhaled breath concentrations

<p><b>Copyright information:</b></p><p>Taken from "PBTK Modeling Demonstrates Contribution of Dermal and Inhalation Exposure Components to End-Exhaled Breath Concentrations of Naphthalene"</p><p></p><p>Environmental Health Perspectives 2007;115(6):894-901.</p><p>Published online 14 Feb 2007</p><p>PMCID:PMC1892111.</p><p>This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI</p> Parameters were adjusted at the 1% level

Schematic of the physiologically based toxicokinetic (PBTK) models for the study of naphthalene toxicokinetics

<p><b>Copyright information:</b></p><p>Taken from "PBTK Modeling Demonstrates Contribution of Dermal and Inhalation Exposure Components to End-Exhaled Breath Concentrations of Naphthalene"</p><p></p><p>Environmental Health Perspectives 2007;115(6):894-901.</p><p>Published online 14 Feb 2007</p><p>PMCID:PMC1892111.</p><p>This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI</p> Pulmonary uptake of naphthalene in the personal breathing-zone and pulmonary clearance from the blood compartment are added to a previously published dermatotoxicokinetic model (). Abbreviations in the PBTK model: , input rate constant for dermal exposure; , permeability coefficient for the viable epidermis; , exposed surface area; , stratum corneum:viable epidermis partition coefficient; , blood flow rate to skin; , viable epidermis:blood partition coefficient; , pulmonary ventilation rate; , blood:air partition coefficient; , blood flow rate to fat; , fat:blood partition coefficient; , blood flow rate to other tissue; , other tissue:blood partition coefficient; , extraction ratio

Plots comparing the PBTK model simulations to experimentally measured naphthalene concentrations in blood from 10 study volunteers () who were dermally exposed to JP-8 on the volar forearm

<p><b>Copyright information:</b></p><p>Taken from "PBTK Modeling Demonstrates Contribution of Dermal and Inhalation Exposure Components to End-Exhaled Breath Concentrations of Naphthalene"</p><p></p><p>Environmental Health Perspectives 2007;115(6):894-901.</p><p>Published online 14 Feb 2007</p><p>PMCID:PMC1892111.</p><p>This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI</p

compMS2Miner: An Automatable Metabolite Identification, Visualization, and Data-Sharing R Package for High-Resolution LC–MS Data Sets

A long-standing challenge of untargeted metabolomic profiling by ultrahigh-performance liquid chromatography–high-resolution mass spectrometry (UHPLC–HRMS) is efficient transition from unknown mass spectral features to confident metabolite annotations. The <i>compMS</i>²<i>Miner</i> (Comprehensive MS² Miner) package was developed in the R language to facilitate rapid, comprehensive feature annotation using a peak-picker-output and MS² data files as inputs. The number of MS² spectra that can be collected during a metabolomic profiling experiment far outweigh the amount of time required for pain-staking manual interpretation; therefore, a degree of software workflow autonomy is required for broad-scale metabolite annotation. <i>CompMS</i>²<i>Miner</i> integrates many useful tools in a single workflow for metabolite annotation and also provides a means to overview the MS² data with a Web application GUI <i>compMS</i>²<i>Explorer</i> (Comprehensive MS² Explorer) that also facilitates data-sharing and transparency. The automatable <i>compMS</i>²<i>Miner</i> workflow consists of the following steps: (i) matching unknown MS¹ features to precursor MS² scans, (ii) filtration of spectral noise (dynamic noise filter), (iii) generation of composite mass spectra by multiple similar spectrum signal summation and redundant/contaminant spectra removal, (iv) interpretation of possible fragment ion substructure using an internal database, (v) annotation of unknowns with chemical and spectral databases with prediction of mammalian biotransformation metabolites, wrapper functions for <i>in silico</i> fragmentation software, nearest neighbor chemical similarity scoring, random forest based retention time prediction, text-mining based false positive removal/true positive ranking, chemical taxonomic prediction and differential evolution based global annotation score optimization, and (vi) network graph visualizations, data curation, and sharing are made possible via the <i>compMS</i>²<i>Explorer</i> application. Metabolite identities and comments can also be recorded using an interactive table within <i>compMS</i>²<i>Explorer</i>. The utility of the package is illustrated with a data set of blood serum samples from 7 diet induced obese (DIO) and 7 nonobese (NO) C57BL/6J mice, which were also treated with an antibiotic (streptomycin) to knockdown the gut microbiota. The results of fully autonomous and objective usage of <i>compMS</i>²<i>Miner</i> are presented here. All automatically annotated spectra output by the workflow are provided in the Supporting Information and can alternatively be explored as publically available <i>compMS</i>²<i>Explorer</i> applications for both positive and negative modes (https://wmbedmands.shinyapps.io/compMS2_mouseSera_POS and https://wmbedmands.shinyapps.io/compMS2_mouseSera_NEG). The workflow provided rapid annotation of a diversity of endogenous and gut microbially derived metabolites affected by both diet and antibiotic treatment, which conformed to previously published reports. Composite spectra (<i>n</i> = 173) were autonomously matched to entries of the Massbank of North America (MoNA) spectral repository. These experimental and virtual (lipidBlast) spectra corresponded to 29 common endogenous compound classes (e.g., 51 lysophosphatidylcholines spectra) and were then used to calculate the ranking capability of 7 individual scoring metrics. It was found that an average of the 7 individual scoring metrics provided the most effective weighted average ranking ability of 3 for the MoNA matched spectra in spite of potential risk of false positive annotations emerging from automation. Minor structural differences such as relative carbon–carbon double bond positions were found in several cases to affect the correct rank of the MoNA annotated metabolite. The latest release and an example workflow is available in the package vignette (https://github.com/WMBEdmands/compMS2Miner) and a version of the published application is available on the shinyapps.io site (https://wmbedmands.shinyapps.io/compMS2Example)